Title: Congenital Ectropion Uveae
Author (s): Samareh Dadashazar, MS IV, Texas Tech University Health Sciences Center School of Medicine
Photographer: James Gilman, CRA, FOPS
Keywords/Main Subjects: Congenital Ectropion Uveae; Secondary Glaucoma
Diagnosis: Congenital Ectropion Uveae
Author: Samareh Dadashazar, MS IV, Texas Tech University Health Sciences Center School of Medicine
Ectropion uveae is a condition where there is migration of the posterior iris pigmented epithelium from the pupillary ruff onto the anterior surface of the iris. This process can either be congenital or acquired. The congenital form is noted to be rare and non-progressive.1 An exact mechanism is currently unknown, but many theories have postulated that a late developmental arrest of posterior neural crest cells plays a role.1,3 Others suggest that there may be a type of primordial endothelium in the anterior chamber that does not fully regress and subsequently induces a hyperplasia of the pigmented epithelium leading to the anterior movement.2,4 In contrast, the acquired form occurs when a membrane develops in the anterior segment secondary to any inflammatory, neoplastic, or ischemic process.1 This membrane eventually contracts, pulling the posterior pigmented epithelium of the iris anteriorly, thus forming the ectropion uvea. As such, the acquired type is considered progressive in nature. The most common causes of acquired ectropion uvea are neovascular glaucoma and neovascularization of the iris.2,3,4
Congenital ectropion uvea is usually a unilateral finding, but bilateral cases have been reported in the literature.4 The ectropion uvea can be an isolated finding, seen alongside ptosis with good levator function, or as part of a systemic disorder such as neurofibromatosis type 1 (NF1), Rieger’s anomaly, and Prader-Willi syndrome.1–5 An extremely important association to be aware of is the one between congenital ectropion uvea and secondary glaucoma. The literature reports up to 80-90% of patients with congenital ectropion uvea will eventually develop glaucoma at some point in their life.2,5 There are approximately 50 established cases of glaucoma secondary to congenital ectropion uvea in the literature.5 Most patients are affected in childhood or early adolescence, but the reported ages have ranged from 7 months to 42 years.2,4,5 The variation in age of presentation likely correlates to the degree of neural crest cell arrest and trabecular meshwork malformation.2,4 While there are a couple of exceptions reported in the literature, the trend seems to be that patients with both congenital ectropion uvea and NF1 develop an angle-closure glaucoma while those without NF1 develop an open-angle glaucoma.1,3,5 In most cases of congenital ectropion uvea without NF1, patients have anterior insertion of the iris, typically at the level of the trabecular meshwork but sometimes as anterior as Schwalbe’s line.2,5 With such anterior insertion, it is clear to see how these open but dysplastic angles predispose these patient to develop glaucoma over time.
Currently, there is not a consensus on what the best treatment is for patients with glaucoma secondary to congenital ectropion uvea. In contrast to primary congenital glaucoma, many articles in the literature have reported that goniotomies and trabeculotomies are not effective for long-term pressure control and that patients who received these interventions subsequently needed a trabeculectomy or cycloablation in order to bring their pressures back down.2,5 The longest reported case of intraocular pressure control due to goniotomy alone is only 2.5 years.5 Glaucoma drainage devices also seem to fail at controlling pressures in these patients.5 Currently, filtering procedures with antifibrotics, such as a trabeculectomy with mitomycin c, seem to be the most successful surgical intervention for managing long-term intraocular pressures in patients with congenital ectropion uvea.5
In conclusion, congenital ectropion uvea is itself a benign condition, however, it’s strong association with the development of glaucoma is important for physicians to be aware of in order to prevent future vision loss in these patients. If a patient is diagnosed with congenital ectropion uvea, regular tonometry evaluations are needed for their entire lifetime in order to monitor intraocular pressures. More extensive long-term follow-up is needed to establish which surgical intervention is the most successful in controlling intraocular pressures in patients with congenital ectropion uvea.
- Harasymowycz, P. J., Papamatheakis, D. G., Eagle Jr, R. C. Wilson, R. P. (2006). Congenital ectropion uveae and glaucoma. Arch Ophthalmol, 124(2), 271-273. doi:10.1001/archopht.124.2.271
- Prenshaw, J. & Salim, S. (2013). Ectropion uveae and secondary glaucoma. Ophthalmic Pearls. Retrieved from https://www.aao.org/eyenet/article/ ectropion-uveae-secondary-glaucoma
- Seymenoglu, G. & Baser, E. (2011). Congenital iris ectropion associated with juvenile glaucoma. International Ophthalmology, 31(1), 33-38. doi: 10.1007/s10792-010-9388-6.
- Shifa, J. Z., Nkomazana, O., Bekele, N. A. , & Kassa, M. W. (2016). A young Botswana patient with congenital iris ectropion uvea. The Pan African Medical Journal, 25(42). doi: 10.11604/pamj.2016.25.42.10593
- Wang, G. M., Thuente, D., & Bohnsack, B. L. (2018). Angle closure glaucoma in congenital ectropion uvea. American Journal of Ophthalmology Case Reports, 10, 215-220. doi: 10.1016/j.ajoc.2018.03.009
Author: Amber Jimenez
Photographer: Moran Eye Center photography
Keywords/Main Subjects: tumor, tumor suppressor, leukocoria, RB1
Retinoblastoma is an intraocular malignancy of the retinal cells resulting from a disruption of a tumor suppressor gene, called RB1. The disease often presents in children within the first two years of life. The most common symptom of retinoblastoma is leukocoria, or white pupil. One, or both eyes may be affected, and extent of the disease may vary, depending largely on the type of mutation being germline or somatic. Left untreated, retinoblastoma may have debilitating effects on vision and can be fatal. Prompt referral for management of the condition is recommended.
Figure 1. A: Heritable RB patient presenting with bilateral leukocoria, the most commonly reported presenting sign of this condition. B: RB cells have a propensity to detach from the primary tumor mass and spread throughout the eye, as illustrated by a patient with endophytic RB who developed marked tumor cells in the vitreous, resembling vitritis. C: Occasionally tumor necrosis may produce an inflammatory response associated with a red eye and conjunctival injection as seen in this patient. The patient also has a tumor hypopyon. D: Massive tumor necrosis in the phthisical eye of a patient with RB has resulted in marked inflammation involving the orbit, simulating an orbital cellulitis with lid swelling and pain on eye movement.
Taken from Figure 26.4 A-D, Hartnett, M.E. (2014) Pediatric Retina. Philadelphia, PA. Lippincott Williams & Wilkins, a Wolters Kluwer business.
Taken from Figure 26.5 B, Hartnett, M.E. (2014) Pediatric Retina. Philadelphia, PA. Lippincott Williams & Wilkins, a Wolters Kluwer business.
Age & Gender: The incidence of retinoblastoma is similar in males and females. Most cases are diagnosed at birth or early infancy, with an average age of diagnosis of bilateral disease at 12 months and 24 months for patients with unilateral disease.
Genotype: Both heritable (germline mutation) and nonheritable (somatic mutation) retinoblastoma arise from mutations in the retinoblastoma gene, RB1, on both alleles of chromosome 13q14.
Symptoms: The most common clinical presentation of retinoblastoma includes symptoms of leukocoria, white pupil, or strabismus in a child under 2 years of age. Other symptoms include nystagmus or a red inflamed eye.
Environmental Factors or Other Considerations: Germline mutations of RB1 have been found to occur on paternally derived chromosomes, suggesting that increased paternal age may have impact on the occurrence of retinoblastoma. No other environmental factors have been identified.
Treatment: Treatment options vary depending on the size and location of the tumor, extent of visual disturbance, optic nerve involvement, and presence of metastatic disease. Surgery, brachytherapy or radiation, chemotherapy, and laser therapy are common treatments.
Pathophysiology: The RB1 gene encodes the Rb protein which functions as a tumor suppressor by restricting progression of the cell cycle in dividing cells. Loss of function in both copies of RB1 causes cell cycle dysregulation, allowing for potentially cancerous cells to continue dividing. The Knudson “two-hit” model differentiates the heritable and nonheritable forms. Patients with the heritable form of retinoblastoma inherit a germline mutation of RB1 in all cells in the body, thus creating the “first hit.” A “second hit” occurs when the second allele of RB1 is mutated or silenced through epigenetic changes, affecting retinal cells. Patients with heritable retinoblastoma are at increased risk for bilateral and multifocal disease. Nonheritable retinoblastoma occurs with somatic mutations of both copies of the RB1 gene (both “first” and “second” hit) in a retinal cell. These patients present with unilateral and unifocal disease, and which usually occurs later in life.
Differential Diagnosis: The most common differential diagnoses include conditions associated with the most common presenting symptom of retinoblastoma, infantile leukocoria. Such conditions include congenital malformations such as persistent fetal vasculature, vascular changes such as Coat’s disease, and inflammatory diseases such as ocular tococariasis. A patient’s age, combined with a consistent clinical presentation, morphologic features, and family history, are key to differentiating these conditions from retinoblastoma.
References: Originally published in: Hartnett, Mary Elizabeth. Pediatric retina: medical and surgical approaches. 2nd Ed. Philadelphia: Lippincott Williams & Wilkins, 2005.
Abramson, D. H., Frank, C. M., Susman, M., Whalen, M. P., Dunkel, I. J., & Boyd, N. W. (1998). Presenting signs of retinoblastoma. The Journal of Pediatrics,132(3), 505-508. doi:10.1016/s0022-3476(98)70028-9
Abramson, D. H., Beaverson, K., Sangani, P., Vora, R. A., Lee, T. C., Hochberg, H. M., Kirszrot, J., Ranjithan, M. (2003). Screening for Retinoblastoma: Presenting Signs as Prognosticators of Patient and Ocular Survival. Pediatrics,112(6), 1248-1255. doi:10.1542/peds.112.6.1248
Balmer A, Munier F. Differential diagnosis of leukocoria and strabismus, first presenting signs of retinoblastoma. Clinical ophthalmology (Auckland, NZ). 2007;1(4):431-439.
Faculty Approval by: M. E. Hartnett, MD
Copyright ©2019. For further information regarding the rights to this collection, please visit: http://morancore.utah.edu/terms-of-use/
Title: A Brief Overview of Keratoconus and its Topographical Findings
Author: Zachary Mortensen, MS4, MBA
Photographer: James Gilman, CRA, FOPS
Date: August 24, 2018
Keywords/Main Subjects: keratoconus, cornea, corneal ectasia, corneal topography, collagen cross-linking
Summary of the Case: Progressive keratoconus in a young patient that is marked by progressive astigmatism, thinning and steepening of the cornea. The patient is monitored with corneal topography. He is an excellent candidate for corneal collagen cross-linking.
A 14-year-old boy with seasonal allergic rhinitis presents with a four-year history of keratoconus in both eyes that continues to progress. He has asymmetric astigmatism and has used prescription glasses in the past, but he now uses rigid gas permeable contact lenses. He has some optic nerve atrophy in the left eye due to a sledding accident trauma seven months ago that is now likely stable. He has no known family history of keratoconus or other eye diseases. He uses preservative free artificial tears as needed for eye dryness and oral antihistamines as needed for allergies.
Upon presentation to our clinic, his best corrected visual acuity with gas permeable contacts was 20/30-2 and 20/60-1 in the right and left eyes respectively. Slit Lamp examination of the anterior segment examination reveals the following image (Figure 1):
Central thinning, Vogt’s striae, and iron rings were appreciated on corneal examination in both eyes, and an apical scar seen in the left eye. The rest of the exam was unremarkable besides temporal sloping and some pallor of the left optic disc, likely due to the history of trauma.
Atlas Corneal Topography
Corneal topography is the gold standard for screening patients for keratoconus. Early screening for keratoconus is helpful because patients often look normal on slit lamp examination. It is also important for monitoring progression.1 Below is a Zeiss Atlas report (Figure 2) of the patient that has both an axial curvature map and a “Rings Image” which is a Placido disc-based topography. The warmer (redder) areas mark the areas of greater steepening.
Calculating an inferior/superior (I-S) value can also be helpful when looking for keratoconus. The ratio of the average power differences between the inferior hemisphere and superior hemisphere on the cornea is the I-S value. A positive value indicates that the inferior cornea is steeper. An I-S value higher than 1.8 has been used by some as the cut-off point for clinical keratoconus.3 If the I-S value is calculated between 1.4 to 1.8, keratoconus can be suspected.3
Scheimpflug tomography (Pentacam)
The patient’s first Scheimpflug tomographic images (Oculus Pentacam) were taken at age 14 (Figure 3). The Pentacam shows several elevation maps. One of the significant advantages of the Pentacam is in its ability to show the posterior elevation changes.4 The elevation maps show an anterior and posterior elevation of the cornea relative to the best fit sphere (BFS). On average, normal anterior elevation change values are between 1 and 2μm, while keratoconic anterior elevation change values are can be 20 μm or greater.4 On average, normal posterior elevation change values are between 2 and 3 μm, while keratoconic posterior elevation change values can be 39-45 μm or greater.4
This patient has keratoconus in both eyes with characteristic progression. The patient has continued to progress when compared to old Atlas and Pentacam images, though manifest refraction has not largely changed. This patient’s keratoconus will likely continue to progress through pubescence and young adulthood.
This patient is encouraged to avoid eye rubbing, which is an associated risk factor.5 It is important to help patients manage anything that can cause them to continue rubbing their eyes, such as prescribing steroids for those with atopic diseases.
When the patient was first seen at 10 years of age, he was managed by correcting visual acuity with spectacles. As he aged, the ectasia progressed, so he then started using rigid gas-permeable contact lenses.
There are also surgical management options that have been discussed with the patient. Intrastromal corneal ring segments are plastic inserts that are implanted into the cornea to flatten it. This can help with the visual acuity but does not stop progression.1 Corneal transplant (keratoplasty) is often used after contact lenses are no longer helpful.1 After discussion, we decided to delay keratoplasty until college-age years in an effort to achieve his best outcome since a higher rate of graft failure has been noted in pediatric penetrating keratoplasties.6
Collagen cross-linking is an intervention approved by the FDA in 2016 that slows the progression of keratoconus by strengthening bonds in the cornea. The procedure involves applying riboflavin (Vitamin B2) drops, then exposing it to ultraviolet light, and a photosensitizer. As it is relatively new in the United States, this procedure may be difficult for patients to acquire health insurance coverage. This patient is a good candidate for collagen cross-linking, so we have worked with him and his insurance company so that he can receive treatment.
Keratoconus, the most common ectatic disease of the cornea, is characterized by progressive central or paracentral thinning and steepening of the cornea such that the cornea takes on the shape of a “cone” (Figure 3). Early-stage keratoconus may look normal on slit lamp examination. Because of this, topography has become the gold standard for screening patients for keratoconus and other corneal ectasias. Topography and tomography are also useful for monitoring disease progression. Regular monitoring can permit early treatments such as corneal collagen cross-linking or corneal transplantation. While each patient should be evaluated individually, collagen cross-linking may be chosen in young patients with progressive keratoconus.
- Wayman, L. L., Trobe, J., Wilterdink, J. L., (2018). Keratoconus. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com (Accessed on August 23, 2018)
- Anderson, D. Understanding Corneal Topography (unknown date). Paraoptometric Resource Center. Retrieved from https://www.aoa.org/Documents/optometric-staff/Articles/Understanding-Corneal-Topography.pdf
- Cavas-Martínez, F., De la Cruz Sánchez, E., Martínez, J. N., Cañavate, F. F., & Fernández-Pacheco, D. G. (2016). Corneal topography in keratoconus: state of the art. Eye and Vision, 3(1), 5.
- Belin, M.W., Khachikian, S. S., Holladay, J. T., Tehrani, M. New Advances and Technology with Pentacam (2008). Highlights of Ophthalmology. Retrieved from https://www.oculus.de/uploads/media/oculus_low_res.pdf
- Sugar, J., & Macsai, M. S. (2012). What causes keratoconus?. Cornea, 31(6), 716-719.
- Bernfeld, E., Epley, K. D., Woodward, M. A. (2017). Pediatric penetrating keratoplasty. EyeWiki. Retrieved from http://eyewiki.aao.org/Pediatric_penetrating_keratoplasty
Faculty Approval by: Mark Mifflin, MD; Griffin Jardine, MD
Copyright statement: Copyright Author Name, ©2018. For further information regarding the rights to this collection, please visit: http://morancore.utah.edu/terms-of-use/
Title: A Cocooned ACIOL Secondary to UGH Syndrome
Author: Tania Padilla Conde, MSIV, University of South Dakota Sanford School of Medicine
Photographer: Dr. Alan Crandall
Image or video:
Keywords/Main Subjects: UGH syndrome, cocooned IOL, uveitis, glaucoma, hyphema
Section 11 lens and cataractà Complications of cataract surgeryà UGH syndrome
Diagnosis: Inflamed cocoon anterior chamber IOL secondary to UGH syndrome, right eye
Description of Image:
This patient is an 85-year-old, African woman who presented with a chief complaint of worsening severe ocular pain in her right eye over the last several months. Her ocular history is significant for uveitis, elevated intraocular pressure (IOP), and cystoid macular edema (CME) of her right eye. Her ocular surgeries include cataract surgery in her right eye involving an anterior chamber intraocular lens (ACIOL) and a second cataract surgery in her left eye 8 years involving a posterior chamber intraocular lens (PCIOL). At presentation, she was on alphagan three times a day and timolol twice a day for her elevated IOP.
On exam, her visual acuity was OD count fingers at 3ft and OS 20/500. IOP by tonometry was OD 12 and OS 10. Pupils were non-reactive OU. Extraocular movements were full and ortho OU. Slit lamp examination OD showed benign melanosis, peripheral anterior synechiae (PAS) and a dislocated cocooned ACIOL. We were unable to get a clear view of the anterior chamber and the iris. We were also unable to get a clear view of the fundus on dilated exam. OS exam was unremarkable.
The patient was subsequently diagnosed with uveitis-glaucoma-hyphema (UGH) syndrome and underwent a removal of the ACIOL, anterior vitrectomy and synechiaelysis of the right eye. Due to severe inflammation, the decision was made to leave the patient aphakic with the possibility of an IOL implant in the future. The explanted IOL was sent to pathology and was found to be a one-piece with haptic PMMA anterior chamber Kelman multiflex-style IOL, Microscopic examination of the IOL showed several small fine granules of pigment on the haptics.
UGH syndrome is a rare condition that classically presents with uveitis, glaucoma, and hyphema in the setting of an anterior chamber IOL. However, it can be diagnosed when one, two, or all three of these conditions are present in the setting of any IOL causing irritation of the iris or angle structures.1 Although it is traditionally seen as a complication of anterior chamber IOLs, single-piece acrylic IOLs or sulcus IOLs, cases with posterior chamber IOLs have also been reported.2 UGH syndrome is commonly characterized by chronic inflammation, CME, secondary iris neovascularization, recurrent hyphemas, and glaucomatous optic neuropathy leading to a loss of vision.3 The diagnosis is clinical, based on the history and physical exam, and can be supplemented by ultrasound biomicroscopy.4
UGH syndrome results from peripupillary contact of the iris with the lens optic/haptics leading to mechanical irritation and erosion of uveal structures. This chafing leads to a breakdown of the blood-aqueous barrier and subsequent release of pigment, red blood cells, protein, and white blood cells into the anterior chamber.5 The resultant inflammation causes uveitis. The release of the red blood cells can additionally cause a hyphema. The increase in IOP is a result of red and white blood cells in the anterior chamber blocking the trabecular meshwork and/or by the destruction of outflow structures. Electron microscopy of explanted IOLs often reveals coccoid-like structures on the haptic surface and melanosomes, likely from damaged iris pigment epithelial cells.6
Medical management can include topical steroids for uveitis, IOP lowering topical and systemic medications for intraocular hypertension, and topical steroids and cycloplegics for hyphema.6 The use of anti-VEGF therapy has been shown to induce the regression of iris neovascularization and inflammation in uveitic macular edema.7 The definitive treatment is often surgical intervention including IOL repositioning, explantation and/or exchange.
- Cheng L, Fox AR, Kam JP, Alward WLM. Uveitis Glaucoma Hyphema (UGH) Syndrome. EyeRounds.org. posted October 3, 2017; Available from: http://EyeRounds.org/cases/257-UGH-syndrome.htm
- Zhang L, Hood CT, Vrabec JP, Cullen AL, Parrish EA, Moroi SE. Mechanisms for in-the-bag uveitis-glaucoma-hyphema syndrome. J Cataract Refract Surg 2014;40(3):490-492. https://www.ncbi.nlm.nih.gov/pubmed/24417893
- Crowell EL. Uveitis-Glaucoma-Hyphema Syndrome. EyeWiki. http://eyewiki.aao.org/ Uveitis-Glaucoma-Hyphema Syndrome. Accessed August 1, 2018.
- Lima BR, Pichi F, Hayden BC, Lowder CY. Ultrasound biomicroscopy in chronic pseudophakic ocular inflammation associated with misplaced intraocular lens haptics. Am J Ophthalmol. 2014 Apr;157(4):813–817. e1. doi: 10.1016/j.ajo.2013.12.025. https://www.ncbi.nlm.nih.gov/pubmed/24398393
- Chang DF, Masket S, Miller KM, Braga-Mele R, Little BC, Mamalis N, Oetting TA, Packer M. Complications of sulcus placement of single-piece acrylic intraocular lenses. Recommendations for backup IOL implantation following Posterior Capsule Rupture. J Cataract Refract Surg 2009;35:1445-58.
- Asaria RH, Salmon JF, Skinner AR, Ferguson DJ, McDonald B. Electron microscopy findings on an intraocular lens in the uveitis, glaucoma, hyphaema syndrome. Eye.1997;11(Pt 6):827–829. https://www.ncbi.nlm.nih.gov/pubmed/9537139
- Ellingson FT. The uveitis-glaucoma-hyphema syndrome associated with the Mark VIII anterior chamber lens implant. J Am Intraocul Implant Soc 1978;4(2):50-53. https://www.ncbi.nlm.nih.gov/pubmed/701165
- Rech L, Heckler L, Damji KF. Serial intracameral bevacizumab for uveitis glaucoma hyphaema syndrome: a case report. Can J Ophthalmol. 2014;49:e160–e162. https://www.ncbi.nlm.nih.gov/pubmed/25433757
Faculty Approval by: Dr. Alan Crandall and Dr. Griffin Jardine
Copyright statement: Copyright Tania Padilla Conde, ©2018. For further information regarding the rights to this collection, please visit: URL to copyright information page on Moran CORE
Disclosure (Financial or other): None
Title: Ophthalmic Manifestations of Mucopolysaccharidosis Type IS (Scheie Syndrome)
Author: Shane Nau M.S., 4th Year Medical Student, University of Colorado School of Medicine
Photographer: Moran Eye Center Photography (Images 1-3), Lydia Sauer MD (Images 4-5)
Date: February 2016 (Images 1-3), June 2018 (Image 5)
Keywords/Main Subjects: Mucopolysaccharidosis; Lysosome Storage Disorder; Metabolic Disease; Corneal Dystrophy; Retinal Degeneration; Retinitis Pigmentosa; RP; Cystoid Macular Edema; CME; Fluoroscein Angiography; FA; Autofluorescence; AF; Fluoroscein Lifetime Imaging Ophthalmoscope; FLIO
Secondary CORE category:
Diagnosis: Mucopolysaccharidosis Type IS (Scheie Syndrome)
Brief Case Description:
The patient is a 37-year-old female referred to retina clinic for evaluation of bilateral cystoid macular edema (CME) in early 2016. Upon presentation she endorsed blurry vision, 3 years of nyctalopia, and 10 years of floaters and scintillations. Her past ocular history is notable for bilateral corneal dystrophy of unknown etiology, which led to a penetrating keratoplasty (PKP) in her left eye. This procedure was complicated by pupillary-block glaucoma that later required cataract surgery. Despite a corneal transplant in the left eye, her vision remained worse in the left eye compared to the right. OCT imaging of her macula was obtained—revealing bilateral CME.
Her past medical history was significant for hand and foot contractures noted since early childhood, mitral valve stenosis noted in adolescence, severe arthritis, and an umbilical hernia that has since been repaired. She has mildly coarse facial features. She does not have a family history of ocular problems or autoimmune disease. She is allergic to Amoxicillin/Penicillin and presented taking both Ilevro (once daily) and Prednisolone (4X daily) eye drops in addition to 20 mg daily oral Prednisone daily.
Eye Exam: (see Image 1)
Vision: 20/60 cc OD and 20/100 cc OS
Pupils: 5>3, hazy view OD and 7>7, irregular OS
External: Normal OU
Slit Lamp: Diffuse corneal clouding OD, PKP OS clear with peripheral corneal clouding
Fundus Exam: Mild hyperemia of disc, CME, Mottled looking periphery OU
CXR: No evidence of Tuberculosis or Sarcoidosis
ACE: 23 (N)
Lysozyme: <0.70 (N)
Retinal Autoantibodies: (+) for 23-kDA HSP27, 28-kDA, 46-kDA Enolase
MPS Urine Quant.: 12.5 (0-7.1)
MPSI Creatinine: 84 (0)
Total GAG Concentration: 11.5 (0-7.1)
Based on the clinical picture outlined above, it becomes clear that this patient presented with a rare combination of bilateral corneal clouding and retinopathy. Each of these respective findings have lengthy differentials. However, assuming these disease processes share a common etiology, the differential is dramatically narrowed. Using this clinical reasoning, we developed a high index of suspicion for more rare diseases such as the Mucopolysaccharidoses (MPS). Subsequently, a more direct and cost-effective workup was initiated. Quickly thereafter, the MPS labs confirmed the diagnosis of MPS Type IS (Scheie Syndrome) allowing the proper treatment regimen to be initiated.
Mucopolysaccharidosis Type IS (MPS IS, Scheie syndrome) is a type of lysosome storage disorder. Most of the mucopolysaccharidoses are mutations that are inherited in autosomal recessive fashion. With regards to Scheie syndrome, the mutation leads to a deficiency in the enzyme α-L-iduronidase, which is responsible for the degradation of glycosaminoglycans (GAG’s) within the body . Without proper functioning of this GAG degradation process, chronic and progressive deposition of GAG’s throughout the body ensues. The eyes are no exception. According to Ashworth et. al., cytoplasmic membrane-bound vacuoles containing GAG’s are found in most ocular tissue (i.e. cornea, conjunctiva, lens epithelial cells, choroid, ciliary body, RPE, ganglion cells, and trabecular endothelium) in MPS IS patients. This extensive GAG deposition in ocular tissues causes structural and functional changes within the eye.
The following ophthalmic findings have been reported in Scheie Syndrome: proptosis, progressive corneal opacification, corneal edema, open angle glaucoma, pupillary- block glaucoma, cataracts, retinitis pigmentosa, and epiretinal membranes . While the ophthalmic findings are essential to an ophthalmologist, it is contextually important to recognize the other clinical features associated with Scheie syndrome when making the diagnosis. According to Beck et al., the following clinical features of Scheie syndrome are ordered from most to least common: corneal clouding, joint contractures, cardiac valve abnormalities, hernias, carpal tunnel syndrome, and coarse facial features . Each of these findings is found in the majority of Scheie syndrome patients. Perhaps more importantly, the patient in this case had each of these findings at some point in her first three decades of life. Had a provider picked up on her unique clinical history, it is possible she may have been diagnosed at a much earlier age.
Traditionally, ophthalmologic treatment of Scheie syndrome has focused on long-term management with conservatively-timed interventions (i.e. PKP for progressive corneal clouding). However, with the more recent advent of gene and enzyme replacement therapy, new options are becoming available for patients. The patient in this case was started on an experimental enzyme replacement therapy and her CME was tracked with serial OCT imaging. While anecdotal, her CME improved throughout treatment and acutely worsened when the study was ended.
Image/Video: Slit lamp (Image 1), OCT of macula (Image 2), Fluorescein Angiography (Image 3), Autofluorescence (Image 4), Fluorescein Lifetime Imaging Ophthalmoscopy (Image 5)
Description of Images:
A 37-year-old patient presented with complaints of blurriness, nyctalopia, and worsened vision in her left eye despite a recent PKP (OS only) for non-specific bilateral corneal dystrophy. She was noted to have bilateral CME and loss of her IS/OS junction on OCT. Autofluorescence and Fluorescence Lifetime Imaging Ophthalmoscopy (FLIO) demonstrated an abnormal ring-shaped pattern around the macula similar to pattern seen with Retinitis Pigmentosa. Operating on the assumption that there was a common etiology for the corneal dystrophy and retinopathy, the diagnosis of mucopolysaccharidoses was suspected and later confirmed with labs. The patient successfully trialed an experimental enzyme replacement therapy and her CME worsened after the funding-based withdrawal of therapy. She has since undergone PKP in right eye as well. She is being followed every 6 months.
Format: Case Report
- Thomas JA, Beck M, Clarke JTR, Cox GF. Childhood onset of Scheie syndrome, the attenuated form of mucopolysaccharidosis I. Journal of Inherited Metabolic Disorders. 2010; 33: 421-427.
- Ashworth J, et al. Mucopolysacharidoses and the Eye. Survey of Ophthalmology. 2006; 51: 1-17.
- Beck M, et al. The Natural History of MPS I: global perspectives from the MPS Registry. Genetics in Medicine. 2014; 16: 759-765.
- Andersen KM, Sauer L, Gensure RH, Hammer M, Bernstein PS. Characterization of retinitis pigmentosa using fluorescence lifetime imaging ophthalmoscopy (FLIO). TVST 2018; 7, 20.
- Lim, J. et al. Retinitis Pigmentosa. Eye Wiki. 23 May 2018, http://eyewiki.aao.org/Retinitis_Pigmentosa#Disease Accessed 20 June 2018
- Van C, Syed NA. Epithelial-Stromal and Stromal Corneal Dystrophies: A Clinicopathologic Review. Revision of [Birkholz ES, Syed NA, Wagoner, MD. Corneal Stromal Dystrophies: A Clinicopathologic Review. Aug. 17, 2009]; EyeRounds.org. August 20, 2015. Available from: http://www.eyerounds.org/cases/43-Corneal-Stromal-Dystrophies.htm
Faculty approval by: Akbar. Shakoor, MD
- Copyright statement: Copyright Author Name, ©2016. For further information regarding the rights to this collection, please visit: URL to copyright information page on Moran CORE
Title: Case Report of Vision Threatening Papilledema due to Idiopathic Intracranial Hypertension
Author: Robert Henseler, 4th Year Medical Student, Rutgers University – New Jersey Medical School
CC: Headache and Blurry Vision
HPI: A 20 y/o obese woman presents with a 2-week history of blurry vision and headaches. She was originally diagnosed with a urinary tract infection and prescribed cefuroxime. After seeing her regular physician, she was referred to an ophthalmologist for her visual symptoms where optic nerve swelling on exam and visual field defects on Humphrey Visual Field (HVF) testing were detected. She also complained of neck pain and photophobia so she was sent to the emergency room to rule out the possibility of meningitis. Ophthalmology was consulted and grade 4 disc edema was noted, showing hemorrhages off the discs, tortuous vasculature, and few macular and peripheral hemorrhages. She also had visual field defects on confrontation testing, a left RAPD, and acuity of 20/100 OD and 20/80 OS. A CT and MRI were performed which suggested increased intracranial pressure. A lumbar puncture (LP) was then performed with opening pressure of 56cm H20. At the time of her first LP, 32ml of CSF were removed and closing pressure was 7cm H20. Patient had some resolution of headache and reported slightly improved vision. Her symptoms returned the next day and a repeat LP done the with 30ml of fluid removed.
Testing During Admission:
LP in Lateral Decubitus Position:
- Opening Pressure 56 cmH20
- No signs of infection
- Flattening of the posterior globes
- Enhancement and intraocular protrusion of the optic nerve heads
- Prominent symmetric optic nerve sheath fluid and enhancement
- Mild symmetric proptosis is suggested
- No mass lesions
- No hemorrhage
- Patent vessels proximally
- Focal narrowing at the bilateral transverse and sigmoid sinus junctions without intraluminal thrombus or evidence of external compression
- Sigmoid sinuses patent distally
The patient was then seen in the neuro-ophthalmology clinic for evaluation.
Neuro-Ophthalmologic History, Exam, and Testing Obtained Day After Admission:
- Located behind her eyes and wrapped around her forehead.
- Started the day following blurry vision and was a sharp pain. 9/10 in severity.
- Originally worse when laying down.
- Pulsatile tinnitus starting 4 days prior to admission.
- Intermittent visual field defects in her left eye when looking straight ahead
- Transient visual obscurations. Her left eye vision was “completely dark” for 2 days prior to admission but it came back on the day before hospital admission.
- Blurry vision in both eyes and constant binocular double vision.
- Tried ibuprofen and acetaminophen but with no relief.
- Morphine given after arrival to the ED, but also provided little to no relief.
- Now after second LP having headaches that are worse when sitting up and better with lying down.
- Patient had no history of migraines, carsickness, nausea, vomiting.
- High School Graduation weight: 170 pounds
- Current weight: Patient thinks 193 pounds but unsure
- Actual weight during admission was 237 pounds
- Maximum weight: Not sure but believes now is her heaviest weight
- COPD: Never smoker
- Venous thrombosis: None
- Steroids use and withdrawal: None
- Oral Contraceptive: Nexplanon implant for the past 2 years
- Vitamin A: None
- Tetracyclines: None
- Isotretinoin: None
- EOMs were full and ortho bilaterally
- Hertel Testing 20, 20 at base 95
- Visual Acuity OD 20/70 -1, OS 20/70. No improvement with pinhole
- Pupil exam was normal except for a RAPD of 0.6 log in the left eye
- Anterior segment exam was normal
- Fundus exam showed grade 3 disc edema with boggy macula and tortuous vessels OU
Patient continued to stay in the Neuro Critical Care Unit. A lumbar drain was placed by neurosurgery after her visit to the ophthalmology clinic. Neuro-ophthalmology continued to follow the patient and it was decided that if she did not have resolution of increased ICP and vision threatening papilledema then a bilateral nerve sheath fenestration would be performed by oculoplastic surgery. Due to lack of improvement the patient underwent surgery on hospital day 3. Her surgery was performed successfully with no complications. Neuro-ophthalmology continued to follow the patient during her stay at the hospital and then manage her care following discharge on hospital day 4. She was discharged on acetazolamide 1000 mg BID to lower CSF production, gabapentin for acetazolamide induced peripheral neuropathy, and hydrocodone/acetaminophen 10/325 for pain.
4 Days after Discharge:
- Headaches improved, occasional headache while upright
- Transient visual obscurations: none
- Pulsatile Tinnitus: resolved
- Vision acuity subjectively improved
- Peripheral Vision: improved
- Diplopia: still had oblique diplopia
- Visual Acuity improved to OD 20/40, OS 20/40 -1
- Left RAPD 0.6 log
- Surgical incisions clean with mild upper eyelid edema
- Anterior segment exam normal
- OD grade 3 edema with punctate hemorrhages peripapillary
- OS grade 3 edema (OS>OD) with peripapillary hemorrhage nasally
- Tortuous vessels OU
- Continue acetazolamide 1000mg BID
- Follow up 1 week
12 Days after Discharge:
- Patient reports worsening symptoms beginning 5 days prior
- Symptoms include nausea, worsened supine headaches, and more pulsatile tinnitus
- Blurry and double vision subjectively worse
- Visual acuity decreased since last visit. 20/60 OD, 20/60+1 OS.
- OD Grade 3 edema, no hemorrhages
- OS Grade 3 edema, superior resolving hemorrhage
- Therapeutic LP now
- Increase acetazolamide to 2000mg BID
- Follow up 1 week
- If not improved will consider shunt placement
18 Days after Discharge:
- Visual fields are subjectively the same for her
- Blurry vision the same
- Double vision almost resolved
- Following LP last visit had improvement of symptoms for 1 day
- Pulsatile tinnitus returned
- Headache continues
- Nausea continues
- On acetazolamide 2000mg BID
- Visual acuity improved to 20/30-2 OD, 20/30-2 OS. No change with pinhole
- Left RAPD 0.3 log
- OD grade 2 edema, no hemorrhages
- OS grade 2 edema, superior resolving hemorrhage
- Tortuous vessels OU
- Still having significant IIH symptoms despite 2000mg BID Diamox
- Side effects almost intolerable
- Visual fields and acuity slightly improved
- Start Lasix 20mg BID trial
- Refer to neurosurgery for shunt placement due to continued IIH symptoms
- Follow up after shunt placement or with worsening symptoms
Discussion of Case:
This was a sudden onset severe case of IIH where many specialties were involved in trying to prevent papilledema induced vision loss. The important aspects of care after admission to the hospital were quick imaging (MRI of the Orbits, Brain and CT Venogram), LP in lateral decubitus, and ophthalmology consultation, examination, and HVF testing. The initially differential diagnosis for increased ICP could include a multitude of pathologic processes.
Differential Diagnosis of Papilledema and Increased ICP:
- Intracranial mass lesion, tumor or hematoma
- Cerebral edema from acute hypoxic ischemic encephalopathy, large cerebral infarction, or traumatic brain injury
- Choroid plexus papilloma causing increased CSF production
- Arachnoid granulation adhesions resulting in decreased CSF absorption
- Obstruction of venous outflow from venous sinus thrombosis or jugular vein compression
- Obstructive hydrocephalus (meningitis, cyst, or Chiari malformation)
- Idiopathic intracranial
The MRI of the orbits, brain, and spine are used to assess for many of these causes as well as the ability to show signs of increased ICP. It is also important to rule out brain herniation which would be a contraindication to LP. The CTV was performed to rule out venous sinus thrombosis. The LP in lateral decubitus position is then used to assess the opening pressure. It is also important to test for infectious causes and meningitis. Quick ophthalmologic consultation is also vital to look at the severity of papilledema and guide management. HVF testing was used to track visual field deficits resulting from papilledema and OCT was used to measure and follow the amount of optic nerve swelling. After all the testing, as well as obtaining a thorough history, the diagnosis of IIH was made with weight gain and obesity as the most likely etiology.
The rapid progression and severity of symptoms in the patient’s clinical course led to more aggressive treatment of her vision threatening papilledema. During her first 2 days in the hospital she had two LPs performed and a drain placed to remove fluid and control pressure. The decision for bilateral optic nerve sheath fenestration—while controversial due to risk of damage to the optic nerve—can be safely performed by a well-trained oculoplastic surgeon and provide significant relief to the optic nerves. Performing optic nerve sheath fenestrations unilaterally is more common. During the case, discussions were made about how best to perform optic nerve sheath fenestration while a patient has a drain. Having fluid surrounding the optic nerve allows for easier and safer surgery but increases the pressure and can cause more damage to the optic nerve. It was decided that moving forward it is best to place the drain at a height so as to maintain a pressure of 20 cmH20 a few hours prior to surgery thus allowing safe surgical approach while minimizing the risk of progressive visual damage.
Since the patient continued to have severe symptoms of increased ICP as well as minimal improvement of OCT and HVF the dose of her acetazolamide was increased to 2000mg BID at day 12 post D/C. This is a large dose and the patient was unable to tolerate the adverse effects of the medication and still continued to have symptoms of increased ICP. While not usually necessary to control optic nerve swelling and IIH symptoms, the decision was made to place a CSF shunt. This was a severe and rapid case of IIH. Aggressive medical and surgical treatment was used in order to minimize optic nerve swelling and symptoms of increased ICP. In summary, severe visual symptoms should always be addressed rapidly by an ophthalmologist as delay can lead to permanent visual deficits. Management should always be individually tailored as not all cases require the same treatment course.
Fundus Photo Right – 4 days post D/C
Fundus Photo Left – 4 days post D/C
Grade 3 papilledema OU with loss of major vessels bilaterally as they exit the disc. The left disc is more edematous than the right. Vessels are tortuous and areas of hemorrhage are seen.
OCT Right – during admission
OCT Right – 4 days post D/C
OCT Right – 12 days post D/C
OCT Right – 18 days post D/C
The edema of the right optic nerve progresses to week day 12 and then begins to resolve slightly by day 18 even though measurements are still above normal limits.
OCT Left – during admission
OCT Left – 4 days post D/C
OCT Left – 12 days post D/C
OCT Left – 18 days post D/C
Optic nerve swelling is more significant in the left eye compared to the right which corresponds to the left RAPD as well as exam findings. It is slightly improved from baseline after 2 LPs, a drain, and optic nerve sheath fenestration, but then progresses again on day 12. By day 18 after 1 week of 2000mg BID acetazolamide it is resolving slightly.
HVF Right – during admission
HVF Right – 4 days post D/C
HVF Right – 12 days post D/C
HVF Right – 18 days post D/C
The HVF on the right shows enlarge blind spots temporally and arcuate defects nasally. There is progression of visual field losses until day 12 post D/C with some improvement by day 18 post D/C. These findings correspond with patient symptoms as well as with OCT measurements.
HVF Left – during admission
HVF Left – 4 days post D/C
HVF Left – 12 days post D/C
HVF Left – 18 days post D/C
The HVF on the left shows enlarge blind spots temporally and arcuate defects nasally that expand past midline temporally. There is progression of visual field losses until day 12 post D/C with some improvement by day 18 post D/C. The visual field defects are more significant in the left eye than the right eye. These findings correspond with exam findings, fundus photographs, and OCT measurements.
Title: Case Report of Idiopathic Intracranial Hypertension and Frisen Scale Papilledema Grading
Author (s): Cole Swiston MSIV, Meagan Seay MD
Photographer: Danielle Princiotta, Becky Weeks
Image or video:
Keywords/Main Subjects: papilledema, idiopathic intracranial hypertension, IIH, papilledema grading
Subcategory: Decreased Vision > Optic Neuropathy
Diagnosis: Idiopathic Intracranial Hypertension
Description of Image:
History of present illness: The patient is a 27-year-old woman, 5 ½ weeks pregnant, who presented to the neuro-ophthalmology clinic with a one-week history of peripheral vision loss in both eyes. She also experienced a left sided throbbing headache, pain behind her eye, and associated neck pain. She had nausea and vomiting during the same time frame. The patient originally presented to an urgent care facility 2 days prior, where the physician noted possible papilledema on exam and transferred her to the emergency room for evaluation. In the ER, the patient underwent lumbar puncture with an opening pressure of 56 cm H2O. CSF glucose, protein, and WBCs were within normal limits. She then underwent an MRI of her head which revealed no structural lesions, acute hemorrhage or infarct though this did show signs of elevated intracranial pressure including bilateral flattening of the posterior sclera and an “empty sella”. An MRV was also performed which showed no evidence of venous outflow obstruction. She was prescribed Diamox but did not begin taking the medication out of fear that it would harm her baby. She had no diplopia, flashers, or floaters in her vision, and had no history of blood clots, though she had 4 prior miscarriages. She was taking an 81 mg aspirin per the recommendation of her obstetric provider and had been on progesterone for the last three weeks during this pregnancy. The patient had no history of doxycycline, tetracycline, steroid, lithium, or Vitamin A derivative use. The last time she was on an oral contraceptive was eight years ago. She weighed 220 pounds and her weight was stable for the past year.
Neuro-ophthalmology examination: The patient’s visual acuity was 20/20 in each eye; her pupils were reactive without a relative afferent pupillary defect. Extraocular movements were full in both eyes, and visual fields performed by confrontation revealed partial inferonasal defect in the right eye. She performed Humphrey 24-2 Visual Field testing which revealed significant peripheral field loss in both eyes, the left eye more so than the right. She identified 11.5/15 Ishihara plates correctly in the right eye, 12.5/13 in the left eye. Slit lamp exam of the anterior segment was unremarkable, and fundus exam revealed grade 4 papilledema in both the right and left (Figure 1) with mild vascular tortuosity. OCT-RNFL confirmed bilateral optic disc swelling.
Clinical Course: The patient was diagnosed with papilledema secondary to idiopathic intracranial hypertension (IIH). After discussing with maternal fetal medicine, it was decided that the benefits of Diamox (Pregnancy Category C) outweighed the risk and the patient agreed to begin taking 500 mg twice a day, increasing to 1000 mg twice a day after two days. Given the severity of her papilledema and visual field defects, the patient was admitted for lumbar drain placement, at which time her opening pressure was 32 cm H2O. The lumbar drain was removed after four days in the hospital. On the day of drain removal, the patient was discharged and seen for follow-up in neuro-ophthalmology clinic. At that time, her visual acuity remained 20/20 in each eye. Papilledema was still present on fundus exam and by RNFL but improved in both eyes, and her objective visual field testing (Humphrey 24-2) showed significantly improved peripheral defects. The patient was continued on Diamox 1000 mg twice a day and was scheduled for close follow up for management of this new diagnosis of IIH.
Discussion: Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a condition of increased intracranial pressure (ICP) of unknown etiology. The disease primarily affects obese women of child bearing age, but other risk factors include obstructive sleep apnea, hypothyroidism, anemia, autoimmune conditions, and specific medication use. These medications include steroids, lithium, oral contraceptives, tetracyclines, and vitamin A derivatives. Common non-ocular symptoms include headache, nausea, vomiting, and pulsatile tinnitus (the sensation of blood flow and “whooshing” in the ears). Ocular symptoms are variable, but generally include visual disturbance, either transient episodes of visual loss with position changes or Valsalva maneuver, or peripheral field defects. Central vision is usually spared until very late in the disease. Diplopia may occur if increased intracranial pressure leads to a unilateral or bilateral sixth cranial nerve palsy.1 The main ocular sign of IIH and increased ICP is papilledema, characterized by bilateral optic disc swelling, elevation, blurring of the disc margins, and obscuration of optic disc blood vessels. The modified Frisén scale has been used to grade the severity of papilledema, summarized in Figure 2.2 If IIH is suspected based on presenting clinical symptoms, the first step in diagnosis is fundoscopy to assess for papilledema. Optical coherence tomography (OCT) can be used to quantify the optic disc swelling, and visual field testing is useful to assess for the degree of peripheral field loss. The next steps in diagnosis involve establishing objective evidence of increased ICP and ruling out other potential etiologies. This is accomplished with neuroimaging, usually an MRI, which excludes structural causes (i.e. mass lesions, hemorrhage, or obstructive hydrocephalus), and MRV to rule out venous outflow obstruction (i.e. dural sinus thrombosis). A lumbar puncture with opening pressures confirms elevated ICP and evaluates for alternative etiologies of elevated ICP, including infection, inflammation, or neoplasm.3 Based on these results, the modified Dandy criteria can be used to establish a diagnosis of IIH:
- Signs and symptoms of increased ICP
- Absence of localizing findings on the neurologic exam, other than sixth nerve palsy
- Awake and alert patient
- Normal neuroimaging findings except for signs of elevated ICP
- Increased CSF opening pressure (>25 cm H2O) with normal CSF composition
- No other cause of elevated ICP found4
The management of IIH consists of both medical and surgical/intervention options depending on the severity of papilledema and symptoms. The mainstay of treatment consists of weight reduction and medical management, usually with acetazolamide. Other diuretics including furosemide are sometimes used alone or in combination with acetazolamide. Interventional options range from large volume lumbar punctures and lumbar drains, which are more temporary measures, to lumboperitoneal (LP) or ventriculoperitoneal (VP) shunts, venous sinus stenting, and optic nerve sheath fenestrations.3
- Markey KA, Mollan SP, Jensen RH, Sinclair AJ. Understanding idiopathic intracranial hypertension: mechanisms, management, and future directions. Lancet Neurol. 2016;15(1):78-91. doi:10.1016/S1474-4422(15)00298-7
- Diagnosis and Grading of Papilledema in Patients With Raised Intracranial Pressure Using Optical Coherence Tomography vs Clinical Expert Assessment Using a Clinical Staging Scale | Neuro-ophthalmology | JAMA Ophthalmology | JAMA Network. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/425762. Accessed September 15, 2018.
- Jensen RH, Radojicic A, Yri H. The diagnosis and management of idiopathic intracranial hypertension and the associated headache. Ther Adv Neurol Disord. 2016;9(4):317-326. doi:10.1177/1756285616635987
- Friedman DI, Liu GT, Digre KB. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013;81(13):1159-1165. doi:10.1212/WNL.0b013e3182a55f17
Faculty Approval by: Griffin Jardine, MD
Footer: Copyright statement: Copyright Cole Swiston, ©2018. For further information regarding the rights to this collection, please visit: URL to copyright information page on Moran CORE
Disclosure (Financial or other): The authors have no financial disclosures.
Title: Custom Implant for Correction of Enophthalmos After Orbital Fracture Repair
Author: Benjamin West, MSIV, Loma Linda University
Image or video:
Keywords/Main Subjects: Orbital fractures, Le Fort fractures, Open Globe, Enophthalmos, Orbital Implant; Porous Polyethylene; Custom Implant
CORE Category: Orbit, Eyelids and Lacrimal System > The Anophthalmic Socket > 4. Orbital Implants > “Custom Implant for Correction of Enophthalmos After Orbital Fracture Repair: Case Report”
Diagnosis: Enophthalmos after orbital fracture repair
Description of Image:
This is a 40 year old male who presented to the emergency department after being struck by a heavy chain in the face at work. Initial examination showed extensive facial lacerations (brow, nose, eyelid and temple) as well as a 1 cm laceration of the right cornea and sclera with expulsion of orbital contents. CT scans at admission showed hemi-Le Fort fractures 1, 2 and 3 on the right side, with a zygomaticomaxillary complex fracture and fracture of all four orbital walls (Figure 1). The left side exhibited a hemi-Le Fort 2 fracture, as well as medial and inferior orbital wall fractures.
Due to the extensive damage to the globe, the patient was subsequently taken to the operating room for enucleation and implantation of an 18 mm porous polyethylene implant by oculoplastics. Plastic surgery completed the facial fracture repair. Floating zygoma fractures were plated and anchored to the frontal bone and the right orbital floor was plated with resorbable material to contain the orbital implant in normal position.
At 5 months post-op the patient was noted to have significant right-sided enophthalmos > 2 mm, as well as a severely sunken superior sulcus. Repeat imaging showed osseous bridging of the majority of facial fractures, but persistent right orbit medial blowout fracture with medial herniation of orbital contents and irregularity of the right orbital floor (Figure 2). At this time the patient was agreeable to undertake enophthalmos repair of the right eye with implantation of a customized porous polyethylene implant.
Fine-cut updated CT images were sent to Stryker where a virtual reconstruction plan was made according to the imaging and surgeon specifications. The orbital implant was made from porous polyethylene using a 3D printer and tailored specifically to the anatomy of the patient (Figures 3 and 4).
The patient was taken to the operating room with oculoplastics where an incision was made in the inferior fornix of the right lower eyelid. Dissection was carried out to the inferior orbital rim with subsequent elevation of the periosteum and periorbita. The custom implant was then inserted into the orbit and positioned to correct the enophthalmos as compared to the left eye. The implant was screwed into place at the inferior orbital rim.
At the following post-op examination significant improvement was noted in the enophthalmos and sunken superior sulcus of the right eye with high patient satisfaction. Mild ptosis was noted of the right eye and the patient was counseled on possible future repair if unimproved.
Faculty Approval by: Doug Marx
- Copyright Moran Eye Center, ©2018. For further information regarding the rights to this collection, please visit: http://morancore.utah.edu/terms-of-use/
Disclosure (Financial or other):
Title: Peripheral Leakage, Avascularity, and Non-perfusion – A Case of Familial Exudative Vitreoretinopathy
Author (s): Blake H. Fortes, MSIV, Florida International University Herbert Wertheim College of Medicine
Photographer: Moran Eye Center
Image or video:
Keywords/Main Subjects: Familial exudative vitreoretinopathy, FEVR, peripheral avascularity, leakage, non-perfusion, neovascularization
Diagnosis: Familial Exudative Vitreoretinopathy
Summary of Case: Patient is a 21 year old female with a diagnosis of a vasoproliferative tumor in the right eye who noted sudden onset of painless drastic decreased visual acuity in the right eye, which had drastically worsened over the last two months and was accompanied by floaters. She denied any photopsias. She has a history of myopia, and has always noticed decreased visual acuity in the right eye. She has no history of eye trauma, or surgery and was born at term, has a normal developmental history, and denied supplemental oxygen use at birth. Family ocular history was significant for a grandmother who had a retinal detachment requiring multiple surgeries. On exam, her visual acuity with correction in the right eye was 20/125 and in the left eye was 20/30 and was noted to have exotropia of the right eye. Her dilated fundus exam in the right eye revealed a tilted, small optic nerve with a vitreal adhesion from the disc to a temporal scar along with macular edema, temporal macular traction, epiretinal membrane, vascular dragging and tortuosity, as well as a fibrotic white lesion at 10 o’clock, surrounded by retinal pigment epithelial changes, and nearby exudates.
Familial Exudative Vitreoretinopathy:
FEVR is a disorder characterized by incomplete vascularization of the peripheral retina typically due to mutations in the Wnt signaling pathway, which is involved in organogenesis and angiogenesis of the eye. These gene mutations include NDP, FZD4, LRP5, and TSPAN12. Novel mutations in ZNF408 and KIF11 have recently been elucidated, but are not involved in the Wnt signaling pathway. The inheritance pattern varies depending on the mutation and may range from autosomal dominant (most commonly), to autosomal recessive, to X-linked recessive or even sporadic, as only 20-40% of patients with FEVR have a positive family history. Therefore, a negative family history does not exclude this diagnosis. This condition is characterized by variable expressivity and asymmetric disease.
The hallmark and most common finding of FEVR is avascularity in the temporal periphery of the retina with associated retinal neovascularization and fibrosis at the junction between the vascular and avascular retina. This fibrosis may result in traction of the macula and retinal vessels, resulting in macular dragging and radial retinal folds. Macular dragging may result in exotropia, as illustrated in this patient. Subretinal exudation, and any type of retinal detachment (rhegmatogenous, tractional, and exudative) may occur as well. Other less common findings associated with this disorder include secondary epiretinal membrane formation, vitreous hemorrhage, secondary glaucoma (neovascular or phacomorphic), retained hyaloid vascular remnants, and persistent fetal vasculature.
Differential diagnosis includes retinopathy of prematurity, Coats’ disease, Norrie’s disease, osteoporosis pseudoglioma syndrome, incontinentia pigmenti, persistent fetal vasculature, vasoproliferative tumor, and ocular toxocariasis.
The staging for FEVR includes:
- Stage 1: avascular periphery
- Stage 2: retinal neovascularization without exudate (A) or with exudate (B)
- Stage 3: extramacular retinal detachment without exudate (A) or with exudate (B)
- Stage 4: subtotal macula-involving retinal detachment without exudate (A) or with exudate (B)
- Stage 5: total retinal detachment
Only patients who have progressed significantly or are at high risk of progression should be treated. In stage 1-2A disease, the avascular retina should be treated with laser photocoagulation to decrease complications related to retinal neovascularization. Retinal detachment should be treated surgically via pars plana vitrectomy, scleral buckle, or a combination of these two approaches. Retinal exudation and neovascularization may also be managed adjunctively via intravitreal anti-VEGF injection prior to surgery. Due to the unpredictable course of FEVR, lifelong monitoring is indicated. Examination of family members is also warranted to reveal previously undiagnosed cases of FEVR.
Format: Case Presentation
- Chen K, Wang N, Wu W. Familial Exudative Vitreoretinopathy. JAMA Ophthalmol. 2017;135(4):e165487. doi:10.1001/jamaophthalmol.2016.5487.
- Gilmour DF. Familial exudative vitreoretinopathy and related retinopathies. Eye. 2015;29(1):1-14. doi:10.1038/eye.2014.70.
- Natung T, Venkatesh P, Thangkhiew L, Syiem J. Asymmetric presentations of familial exudative vitreoretinopathy. Oman Journal of Ophthalmology. 2013;6(2):129-130. doi:10.4103/0974-620X.116661.
- Ranchod TM, Ho LY, Drenser KA, Capone A, and Trese MT. Clinical presentation of familial exudative vitreoretinopathy. Ophthalmology. 2011;118(10):2070-2075.
- Shastry, B. S. (2009), Persistent hyperplastic primary vitreous: congenital malformation of the eye. Clinical & Experimental Ophthalmology, 37: 884-890. doi:10.1111/j.1442-9071.2009.02150.x
- Shields CL, Kaliki S, Al-Dahmash S, et al. Retinal Vasoproliferative TumorsComparative Clinical Features of Primary vs Secondary Tumors in 334 Cases. JAMA Ophthalmol. 2013;131(3):328–334. doi:10.1001/2013.jamaophthalmol.524
- Sızmaz S, Yonekawa Y, T. Trese M. Familial Exudative Vitreoretinopathy. Turkish Journal of Ophthalmology. 2015;45(4):164-168. doi:10.4274/tjo.67699.
- Tauqeer Z, Yonekawa Y. Familial exudative vitreoretinopathy: Pathophysiology, diagnosis, and management. Asia Pac J Ophthalmol (Phila). 2018;7(3):176-182.
Faculty Approval by: Dr. Albert Vitale
- Copyright statement: Copyright Author Name, ©2016. For further information regarding the rights to this collection, please visit: URL to copyright information page on Moran CORE
- Attribution/citation suggestions
Disclosure (Financial or other): None
Title: Hydrogel Intraocular Lens Opacification and Calcification Pathology using a MemoryLens Model
Author(s): Jed H Assam, M.S., and Nick Mamalis, MD
Photographer: Jed H Assam
Location in Core: Lens and Cataract > Complications of Cataract Surgery > Complications of IOL Implantation
Keywords / Main Subjects: IOL Calcification, IOL Opacification, MemoryLens, Hydrogels, Hydrophilic Acrylic
Diagnosis / Differential Diagnosis: Posterior Capsular Opacity, Soemmering’s Ring, Anterior Capsule Contraction Syndrome (ACCS)/Capsular Phimosis, Anterior Vitreous Floaters
Intraocular lens (IOL) opacification and calcification represent uncommon, but noteworthy causes of blurry vision and decreased visual acuity in pseudophakic patients. Awareness of this pathology becomes particularly important when considering the consequences of reflexively performing initial, errant procedures (nd:YAG and vitrectomy) directed at more common anatomic sources of visual disturbance in pseudophakic populations that typically includes the capsular bag or hyaloid.1,3 A survey (n = 142) evaluating foldable IOL complications requiring removal or secondary interventions identified IOL opacification as a minor cause of postoperative complication in most lens categories evaluated.6 However, for hydrogel (hydrophilic acrylic) IOLs, which represented 4% of the IOLs used in the study, post-operative opacification/calcification was the most common reason for lens removal.6
An explanted, calcified, posterior chamber IOL, MemoryLens (Ciba Vision Corp., Duluth, GA, USA), has been demonstrated in Figure 1. The MemoryLens is a 3-piece foldable hydrogel that was initially released in 1994.3,4 It has been the most heavily documented IOL with postoperative calcification complications in the United States.6 Several other hydrophilic acrylic lenses have also been implicated in calcific opacification as well (Hydroview, Bausch & Lomb; AquaSense, Ophthalmic Innovations International; SC60B-OUV, Medical Development Research).4,7
The time required from initial lens placement to the development of visually significant opacification in hydrogel lenses can take several years.1,7 The mean interval for the MemoryLens IOL was identified by one study examining 106 explanted lenses to be 25.8 ±11.9 months with a range from approximately 3 months to 6 ½ years.1
MemoryLens predisposition to opacification was believed to be related to the buffering process of the lenses manufactured through the year 1999.1,3,4 The mechanism by which granular calcific opacification (Figure 2) occurs in vivo remains unknown. It is presently believed to be a multifactorial event related to the surface ionization of hydrogel under physiologic pH levels which facilitate calcium precipitation.4,7
Some of the risk factors that have been associated with hydrogel IOL calcifications include exposure to surgically introduced exogenous substances such as gas, air, tissue plasminogen activator, and silicone oil. Other risk factors include contact with lens packaging materials and lens polishing techniques.1,8 It is currently unknown whether the direct contact of surgical exogenous substances to the optical surface facilitates calcium precipitation or if such sequela is a consequence of increased inflammation resulting from surgical manipulation.7 Progressive visual loss is the most common primary symptom complaint identified in patients with calcified IOLs.6,7
Diagnostically, the presence of calcium may be confirmed on pathologic analysis post-explantation by observing characteristic histochemical staining of granules with Alizeran (1,2-dihydroxyanthraquinone) red, as shown in Figure 2 and Figure 3c, and by electron microscopy coupled with energy dispersive x-ray spectroscopy.8 Diffuse granular deposition is typically noted over the lens body, but tends to be more heavily concentrated on the optic center. In the MemoryLens the coated anterior surface shows heavier calcification than the posterior surface which shows less. Early on the posterior surface typically remains free of deposits (Figure 2b and d).3,4 For hydrogel lenses in general, calcium deposition distribution may be superficial, intralenticular, or both.7
The only treatment currently available for resolving situations of an opacified calcific IOL includes explantation.5
- Werner L. Causes of intraocular lens opacification or discoloration. Cataract Refract Surg. 2007;33:713-726
- Werner L. Biocompatability of intraocular lens materials. Current Opinion in Ophthalmology. 2008;19:41-49
- Haymore J, Zaidman G, Werner L, Mamalis N, Hamilton S, Cook J, Gillette T. Misdiagnosis of hydrophilic acrylic intraocular lens optic opacification: Report of 8 cases with the MemoryLens. Ophthalmology. 2007;114(9):1689-1695
- Neuhann IM, Werner L, Izak AM, Pandey SK, Kleinmann G, Mamalis N, Neuhann TF, Apple DJ. Late postoperative opacification of a hydrophilic acrylic (hydrogel) intraocular lens. Ophthalmology. 2004;111:2094-2101
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