Title: Advancing Wavelike Epitheliopathy: A subtype of partial limbal stem cell deficiency
Author (s): William B. West Jr.
Photographer: Photos courtesy of Dr. Majid Moshirfar
Keywords/Main Subjects: Advancing Wavelike Epitheliopathy, Partial Limbal Stem Cell Deficiency, Limbal Stem Cell Deficiency, Epitheliopathy
External Disease and Cornea > Clinical Approach to Ocular Surface Disorders > Limbal Stem Cell Deficiency > Advancing Wavelike Epitheliopathy
Diagnosis: Advancing Wavelike Epitheliopathy
Description of Image:
Advancing Wavelike Epitheliopathy (AWE) is a form of ocular surface disorder that was first described by D’Aversa et. al. in 1997. It is characterized by a well-defined epithelial plaque with a rough, wavelike appearance and punctate pattern on fluorescein staining. A sub-epithelial haze may also be present. The plaque arises from the corneal limbus, most often superiorly, and expands toward the visual axis. Patients present with a history of progressive vision loss over a period of several months, as well as ocular irritation and foreign body sensation.
While the exact pathophysiology is poorly understood, AWE is presumed to be a subtype of partial limbal stem cell deficiency (PLSCD). The limbal stem cells are the progenitors of the corneal epithelium and reside at the limbus. Epithelial cells migrate from the limbus toward the center of the cornea, forming the corneal surface. In a limbal stem cell deficiency, some or all of the limbal stem cells become dysfunctional and fail to produce normal epithelium. This process most commonly results in breakdown of the epithelial layer causing surface inflammation, which in turn causes neovascularization or conjunctival invasion of the cornea.
In contrast, in AWE the epithelial surface becomes abnormal but does not break down and conjunctivalization does not usually occur. AWE has been associated with a history of ocular trauma, surgery, or chemical or toxic exposure to the ocular surface.
While the potential differential diagnosis for this disorder is broad, likely considerations include:
- Epithelial ingrowth
- Dry eye disease
- Diffuse Lamellar Keratitis (DLK)
- Central Toxic Keratopathy (CTK)
- Limbal Stem Cell Deficiency (LSCD)
- Ocular Surface Squamous Neoplasia
- Conjunctival Intraepithelial Neoplasia
- Herpes Keratitis
Initial treatment for this disease incudes conservative measures to reduce inflammation and maximize healing. These treatments include artificial tears, oral doxycycline, or topical corticosteroids. Superficial keratectomy can be used, and usually provides temporary resolution of the plaque; however, the plaque nearly always recurs. Adding topical silver nitrate, applied via cotton swab to the affected area after corneal debridement, appears to produce stable recovery. Simple limbal stem cell transplant can be performed to regenerate the corneal limbus, if silver nitrate is unsuccessful. This is usually performed by harvesting limbal stem cells from the unaffected eye (if the disease is not bilateral). Interferon alpha-2b, topical or oral cyclosporine, punctal plugs, scleral lenses, vitamin A, autologous blood serum, amniotic membrane drops, and fluorometholone may be helpful in treating AWE, as they have been used successfuly in treating other varieties of PLSCD. Topical corticosteroids have not been shown to be effective.
This video shows the left eye of a 36-year-old male with a six-month history of vision loss and foreign body sensation after LASIK. Before surgery, he had a history of chronic redness and irritation in the left eye before surgery, as well as a possible chemical injury to that eye as a child. The classic wavelike plaque can be seen advancing from the limbus both inferiorly and superiorly.
Advancing Wavelike Epitheliopathy is a type of partial limbal stem cell deficiency forming a characteristic wavy epithelial plaque that expands from the limbus toward the visual axis. It is associated with injury to the limbal stem cells and is treated with superficial keratectomy and silver nitrate or limbal stem cell transplant. Prognosis is typically excellent after treatment.
- D’Aversa G, Luchs JL, Fox MJ, Rosenbaum PS, Udell IJ. Advancing wave-like epitheliopathy: Clinical features and treatment. Ophthalmology [Internet]. American Academy of Ophthalmology, Inc; 1997;104(6):962–969. Available from: http://dx.doi.org/10.1016/S0161-6420(97)30199-7 PMID: 9186437
- Rossen J, Amram A, Milani B, et al. Contact Lens-induced Limbal Stem Cell Deficiency. Ocul Surf. 2016;14(4):419-434. doi:10.1016/j.jtos.2016.06.003
- Kim BY, Riaz KM, Bakhtiari P, et al. Medically Reversible Limbal Stem Cell Disease: Clinical Features and Management Strategies. Ophthalmology. 2014;121(10):2053-2058. doi:10.1016/j.ophtha.2014.04.025
- Moshirfar M, Hastings JP. Unilateral progressive epitheliopathy after LASIK [Internet]. Journal of Cataract and Refractive Surgery. Lippincott Williams and Wilkins; 2020 [cited 2020 Aug 25]. p. 646–651. Available from: https://pubmed.ncbi.nlm.nih.gov/32271301/ PMID: 32271301
- Tan JCK, Tat LT, Coroneo MT. Treatment of partial limbal stem cell deficiency with topical interferon α-2b and retinoic acid. Br J Ophthalmol. 2016;100(7):944-948. doi:10.1136/bjophthalmol-2015-307411
- Majid Moshirfar MD., William B. West jr., Yasmyne C. Ronquillo. Advancing Wavelike Epitheliopathy. Statpearls. 2020. https://pubmed.ncbi.nlm.nih.gov/32119296/
- William B. West jr., Yasmyne C. Ronquillo, Majid Moshirfar MD. Advancing Wavelike Epitheliopathy. Eyewiki. 2020.
Faculty Approval by: Griffin Jardine, MD
- Copyright statement: Copyright William B. West Jr., ©2020. For further information regarding the rights to this collection, please visit: URL to copyright information page on Moran CORE
- Identifier: Moran_CORE_29777
Disclosure (Financial or other): Nothing to disclose.
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
- Werner L. Calcification of hydrophilic acrylic intraocular lenses. Am J. Ophthalmol. 2008;146(3):341-343
- Mamalis N, Brubaker J, Davis D, Espandar L, Werner L. Complications of foldable intraocular lenses requiring explantation or secondary intervention—2007 survey update. J Cataract Refract Surg. 2008;34:1584-1591
- Gartaganis SP, Prahs P, Lazari ED, Gartaganis PS, Helbig H, Koutsoukos PG. Calcification of hydrophilic acrylic intraocular lenses with a hydrophobic surface: laboratory analysis of 6 cases. Am J Ophthalmol. 2016;168:68-77
- Werner L, Wilbanks G, Ollerton A, Michelson J. Localized calcification of hydrophilic acrylic intraocular lenses in association with intracameral injection of gas. J Cataract Refract Surg. 2012;38:720-721
Title: Crocodile Shagreen corneal dystrophy
Author (s): Tanner Ferguson, MSIV, University of South Dakota Sanford School of Medicine, Jeff Pettey, MD, Moran Eye Center, University of Utah
Photographer: James Gilman
Keywords/Main Subjects: Cornea, corneal mosaic dystrophy, crocodile shagreen
Diagnosis: Crocodile shagreen corneal degeneration
Image 1: On this anterior view of the cornea, the polygonal pattern of opacities with well demarcated intervening clear spaces is visualized.
Image 2: This photo enables the viewer to appreciate the resemblance to crocodile skin and the distinct appearance of the degenerative disorder.
Image 3: In this photo, the intervening clear spaces amongst the opacities are well visualized and the “scaly” appearance is appreciated. Furthermore, the image permits the viewer to appreciate that it likely involves the posterior portion of the corneal stroma.
Summary of the Case:
A 67 year-old female with past medical history significant for Type II diabetes mellitus presented with blurry vision of 6 months onset that is worse at distance. She also complained of glare at night and difficulty with oncoming headlights while driving. Her BCVA is 20/50 in her right eye and 20/60 in her left eye; her BAT is 20/70 and 20/80 in her right and left eye. On exam, her cataracts were graded as 2+ NS (nuclear sclerotic) and 2+ cortical spoking OU. Her cornea also demonstrated a polygonal pattern of opacities in the posterior stroma with clear intervening spaces, resembling a “crocodile skin.” The clinician did not feel her visual complaints were related to the corneal findings revealed on exam and the findings were documented as crocodile shagreen.
Crocodile shagreen background
Crocodile shagreen is a clinical finding that was initially described in the 1920’s and named by Vogt in 1930.1 The disorder is characterized by a grayish, polygonal pattern of opacities with intervening clear zones across the central cornea that resembles crocodile skin.1,2 Although it is classically found in the central visual axis in the cornea, patients are often asymptomatic. It is a benign, degenerative disorder and is commonly found in the elderly population.3
The pathogenesis of the finding remains unknown. It is typically found in the posterior two-thirds of the corneal stroma. Studies with histopathology have reported the presence of clusters of vacuoles and a sawtooth-like configuration of the lamellar collagen in the corneal stroma3-5. Krachmer et al.5 proposed that this irregular collagenous arrangement in the posterior stroma observed on transmission electron microscopy is thought to contribute to the clinical appearance of the finding under the slit lamp. Furthermore, this report suggested that vision is unaffected because the anterior corneal surface is regular. Although the pathogenesis remains unclear, studies have suggested that the presence of vacuoles amongst degenerating keratinocytes is evidence of a degenerative process.2
Central cloudy dystrophy of François (CCDF) is a disease entity with a similar clinical appearance. However, CCDF is distinguished from crocodile shagreen by its autosomal dominant inheritance pattern and may be seen in younger patients.6 The diagnosis of CCDF may be more appropriate if numerous family members present with similar corneal mosaic patterns.2
Currently, the significance of this finding remains unclear. Because it is an incidental and benign finding, it is likely underreported. Although it has been reported with other ocular disease entities in isolated cases, there is no clear association5-7. Future studies are needed to contribute to the understanding and significance of this disorder.
Faculty Approval by: Jeff Pettey, MD
- Vogt A. Lehrbuch Und Atlas Der Spaltlampenmikroskopie Des Lebenden Auges: Mit Anleitung Zur Technik Und Methodik Der Untersuchung. Technik Und Methodik. …. 1930.
- Belliveau MJ, Brownstein S, Agapitos P, Font RL. Ultrastructural Features of Posterior Crocodile Shagreen of the Cornea. Survey of Ophthalmology. 2009;54(5):569-575. doi:10.1016/j.survophthal.2009.02.022.
- Meyer JC, Quantock AJ, Kincaid MC, Thonar EJMA, Hageman GS, Assil KK. Characterization of a Central Corneal Cloudiness Sharing Features of Posterior Crocodile Shagreen and Central Cloudy Dystrophy of Francois. Cornea. 1996;15(4):347.
- Karp CL, Scott IU, Green WR, Chang TS. Central cloudy corneal dystrophy of François: a clinicopathologic study. Archives of …. 1997.
- Krachmer JH, Dubord PJ, Rodrigues MM, Mannis MJ. Corneal Posterior Crocodile Shagreen and Polymorphic Amyloid Degeneration: A Histopathologic Study. Arch Ophthalmol. 1983;101(1):54-59. doi:10.1001/archopht.1983.01040010056008.
- Bramsen T, Ehlers N, Baggesen LH. CENTRAL CLOUDY CORNEAL DYSTROPHY OF FRANÇOIS. Acta Ophthalmologica. 1976;54(2):221-226. doi:10.1111/j.1755-3768.1976.tb00435.x.
- Woodward M, Randleman JB, Larson PM. In Vivo Confocal Microscopy of Polymorphic Amyloid Degeneration and Posterior Crocodile Shagreen. Cornea. 2007;26(1):98-101. doi:10.1097/01.ico.0000240103.47508.c4.
Title: Optic Nerve and Macular OCT in Hurler Syndrome (MPS I)
Author (s): Marshall J. Huang, BS
Photographer: Glen Jenkins
Keywords/Main Subjects: Hurler syndrome, Mucopolysaccharidosis, MPS, Optic disc edema
Diagnosis: Mucopolysaccharidosis Type I – Hurler Syndrome
Description of Image:
The images above include a photos of the optic nerve and SD-OCT of the macula in an 18-month male with a severe form of Mucopolysaccharidosis Type I (MPS I), also known as Hurler Syndrome. MPS I is an autosomal recessive, progressive, multisystem disorder caused by an absence or deficiency of the lysosomal enzyme α-L-iduronidase. This leads to a buildup of glycosaminoglycans within the lysosomes, resulting in a cascade of intracellular events that causes tissue damage and multi-organ dysfunction. This disease comprises of a spectrum of phenotypes, generally classified as Hurler (severe), Hurler-Scheie (intermediate), and Scheie (mild) syndromes.
Common systemic manifestations of Hurler syndrome include gargoyle facies, hepatospenomegaly, impaired cognitive development, dysostosis multiplex, and cardiorespiratory problems. Ocular manifestations include corneal opacification, pigmented retinopathy, central foveal ELM thickening, parafoveal IS/OS thinning, open angle glaucoma, and optic disc edema and atrophy. These symptoms can be delayed or even temporarily reversed using enzyme replacement therapy and hematopoietic stem cell transplant (HSCT).
This patient already received a HSCT but still had significant corneal clouding, as well as craniomegaly and hepatosplenomegaly. In order to evaluate the patient’s degree of retinal involvement, an exam under anesthesia was performed. Indirect ophthalmoscopy and photos of the optic nerve revealed significant disc edema in the left eye, a common finding in Hurler syndrome. In addition, SD-OCT of the macula showed early central foveal ELM thickening, greater in the left eye compared to the right. We also performed an electroretinogram (ERG) and visual evoked potentials (VEP). Those studies revealed significantly decreased flash ERG, 30Hz ERG, and flash VEP signals, with the left eye more attenuated than the right eye.
- Parini R, Deodato F, Di Rocco M, et al. Open issues in Mucopolysaccharidosis type I-Hurler. June 2017:1-9. doi:10.1186/s13023-017-0662-9.
- Ana Maria Martins MD P, Ana Paula Dualibi MD P, Denise Norato MD P, et al. Guidelines for the Management of Mucopolysaccharidosis Type I. The Journal of Pediatrics. 2009;155(S):S32-S46. doi:10.1016/j.jpeds.2009.07.005.
Faculty Approval by: David C. Dries, MD; Griffin Jardine MD
Disclosure (Financial or other): None
Title: Limbal Stem Cell Deficiency
Author: Alex Wright, BS
Keywords/Main Subjects: Limbal Stem Cell Deficiency
Diagnosis: Limbal Stem Cell Deficiency
Description of Image: Limbal Stem Cell Deficiency (LSCD) occurs when the regenerative capacity of the corneal stem cells is impaired or damaged. The Palisades of Vogt, papilla-like structures of the limbus, are densely packed with basal cells, 10-15% of which are thought to be corneal stem cells. When these cells are damaged, the regenerative capacity of the cornea is gone. Thoft and Friend in 1983 originally hypothesized cell division in limbus plus further division of transit amplifying cells during their migration superficially and vertically equaled the amount of mature corneal stem cells lost and sluffed off in the tear film. As the cells are lost, the corneal surface begins to breakdown, which leads to further inflammation, conjunctival ingrowth, and subsequent neovascularization. Clinical symptoms include: photophobia, pain, conjunctivalization, corneal neovascularization, and recurrent ulceration. A diagnosis is established with clinical signs and symptoms and can be confirmed in some cases with impression cytology. Impression cytology looks for the presence of goblet cells on the cornea and helps identify conjunctivalization of the cornea, which is regarded as the most reliable diagnostic sign.
Pterygia can cause LSCD, but also must be differentiated from LSCD. Pterygia are often secondary to sun exposure and occur most commonly nasally. Pterygia are also more likely to be identified in younger patients. LSCD with pterygia are more likely bilateral and located in areas not exposed to the sun as often (notably inferiorly and superiorly). LSCD also occurs more commonly over the age of 50.
Etiologies of LSCD include: idiopathic, chemical/thermal burns, iatrogenic, autoimmune, and congenital/hereditary. Management initially if mild is aimed at controlling inflammation and the progression of the disease with topical steroids and topical cyclosporine drops. In severe cases surgery is often necessary to restore normal corneal epithelium. Many surgical procedures have been identified and studied, including: Conjunctival Limbal Autograft, Simple Limbal Epithelial Transplantation, Cultured Limbal Epithelial Transplantation, Living-Related Conjunctival Limbal Allograft, and Keratolimbal Allograft. When possible an autograft is preferred since allografts require systemic immunosuppression.
These images were taken from a 74-year-old Caucasian male with LSCD bilaterally. These images show a pterygium over the nasal cornea bilaterally and over the temporal cornea on the left eye. There is also signs of conjunctivalization and neovascularization inferiorly bilaterally.
- Dua H S, Saini J S, Azuara-Blanco A, Gupta P. Limbal stem cell deficiency : Concept, aetiology, clinical presentation, diagnosis and management. Indian J Ophthalmol 2000;48:83-92
- Osei-Bempong C, Figuieredo FC, Lako M. The limbal epithelium of the eye – A review of limbal stem cell biology, disease and treatment. Bioessays 2012;35:211-219.
- Hatch KM, Dana R. The Structure and Function of the Limbal Stem Cell and the Disease States Associated With Limbal Stem Cell Deficiency. Int Ophthalmology Clin 2009;49:43-52
- Thoft RA, Friend J. 1983. The X, Y, Z hypothesis of corneal epithelial maintenance. Invest Ophthalmol Vis Sci 24: 1442–3.
- Kim KW, Mian SI. Diagnosis of Corneal Limbal Stem Cell Deficiency. CO-Ophthalmology 2017;28(4):355-362.
- Vadrevu VL, Fullard RJ. Enhancements to the conjunctival impression cytology technique and examples of applications in a clinico-biochemical study of dry eye. CLAO J 1994; 20:59–63.
- Holland EJ. Management of Limbal Stem Cell Deficiency: A Historical Perspective, Past, Present, and Future. Cornea 2015;34:S9-15.
Faculty Approval by: Dr. Brian Zaugg
Disclosure (Financial or other): None
Title: Fundus photo and OCT of Best’s vitelliform macular dystrophy (BVMD)
Author (s): Gavin Gorrell, 4th Year Medical Student, University of New Mexico School of Medicine
Keywords/Main Subjects: Best’s Disease; Best’s vitelliform macular dystrophy (BVMD); bestrophinopathies
Secondary CORE Category: Home / Retina and Vitreous / Hereditary Retinal and Choroidal Dystrophies
Diagnosis: Best’s vitelliform macular dystrophy (BVMD)
Description of Image:
- Egg-yolk appearance of lipofuscin accumulation at the central macula
- Subretinal fluid and lipofuscin accumulation causing RPE detachment
Pathogenesis (&Presentation): Best vitelliform macular dystrophy (BVMD) is the second most common hereditary macular dystrophy and is autosomal dominant with variable penetrance and expression. BVMD is the most common of the “bestrophinopathies”, a group of diseases which all contain various mutations to the BEST1 gene. BEST1 (previously termed VMD2), codes for bestrophin 1, a transmembrane protein in the RPE believed to be involved in anion transport and calcium signaling. Through unclear mechanisms, dysfunction of bestrophin 1 in BVMD leads to accumulation of lipofuscin (a retinal breakdown pigment) between Bruch’s membrane and RPE. This debris leads to the characteristic subretinal egg-yolk lesion.
Presentation: In early disease, usually beginning between ages 3 and 15, fundoscopy shows significant vitelliform (vitellus is latin for egg-yolk) lesions to the central macula, however patients may be asymptomatic or have only minimal loss in visual acuity. Over time the lipofuscin in the initial lesions disperses and is resorbed, leading to a “scrambled egg” appearance. A slow progression to RPE atrophy is expected with vision loss typically stabilizing around 20/30-20/200. Rapid decline in VA should cause concern for choroidal neovascularization, a feared complication that occurs in about 20% of patients (eyewiki).
Diagnosis & Differential:
Diagnosis is primarily made with family history and clinical appearance. Electro-oculography (EOG), which demonstrates abnormally low light/dark ratio in Best’s disease (<1.5), is often obtained to confirm the diagnosis. Genetic testing for BEST1 mutation is also available. Providers should consider OCT and/or fluorescein angiography to evaluate for choroidal neovascularization.
DDx: Adult-onset vitelliform macular dystrophy, toxoplasmosis retinochoroiditis, AMD, Bull’s eye maculopathy
Management: There is no current treatment available for Best’s disease, however patients should be monitored for choroidal neovascularization.
Freund, K. Bailey, David Sarraf, William F. Mieler, and Lawrence A. Yannuzzi. “Hereditary Chorioretinal Dystrophies.” In The Retinal Atlas, 2nd ed., 13–231. Philadelphia, PA, 2017. https://www-clinicalkey-com.libproxy.unm.edu/#!/content/book/3-s2.0-B9780323287920000028?scrollTo=%23hl0000946.
Johnson, Adiv A., Karina E. Guziewicz, C. Justin Lee, Ravi C. Kalathur, Jose S. Pulido, Lihua Y. Marmorstein, and Alan D. Marmorstein. “Bestrophin 1 and Retinal Disease.” Progress in Retinal and Eye Research 58 (May 2017): 45–69. doi:10.1016/j.preteyeres.2017.01.006.
MacDonald, Ian M., and Thomas Lee. “Best Vitelliform Macular Dystrophy.” In GeneReviews(®), edited by Roberta A. Pagon, Margaret P. Adam, Holly H. Ardinger, Stephanie E. Wallace, Anne Amemiya, Lora JH Bean, Thomas D. Bird, et al. Seattle (WA): University of Washington, Seattle, 1993. http://www.ncbi.nlm.nih.gov/books/NBK1167/
“The Electroretinogram and Electro-Oculogram: Clinical Applications by Donnell J. Creel – Webvision.” Accessed June 24, 2017. http://webvision.med.utah.edu/book/electrophysiology/the-electroretinogram-clinical-applications/.
“Best Disease – EyeWiki.” Accessed June 24, 2017. http://eyewiki.aao.org/Best_Disease
Faculty Approval by: Griffin Jardine, MD
Disclosure (Financial or other): None
Multimodal imaging of choroidal metastases from adenoid cystic carcinoma of the submandibular gland.
Title: Multimodal imaging of choroidal metastases from adenoid cystic carcinoma of the submandibular gland.
Author: Brian M. Besch
Keywords/Main Subjects: adenoid cystic carcinoma, choroidal metastasis, ophthalmic pathology, intraocular tumors
Diagnosis: adenoid cystic carcinoma of left submandibular gland with bilateral choroidal metastases
Description of Image: Adenoid cystic carcinoma (ACC) is a rare malignancy originating from multiple sites, but typically arises in the head and neck, and most commonly the salivary glands. Histologically, the lesion is composed of epithelial and myoepithelial cells in three configurations – tubular, cribiform, or solid; the latter is the most aggressive type. The malignancy generally arises between ages 40-60 and has an indolent, but nonetheless persistent course generally refractory to treatment. Initial management is wide surgical resection, typically followed by adjuvant external beam radiation or chemotherapy with cisplatin or melphalan. Distant metastases are common later in the disease course; one report indicates a mean of 48 months following initial management. Metastasis to the lung is most common. Choroidal metastases are rare; at the time of writing, the associated images represent the seventh reported case in the literature. While the limited reports of ACC in general suggest a slight female predominance, of the 6 cases involving choroidal metastases previously described, 5 were in women. All 5 primary tumors arose from submandibular glands, while the single male case derived from the hard palate.
The images represent bilateral choroidal ACC metastases from a 57 year old female. The fundus montage illustrates two metastatic lesions in the left eye; one involves the macula, and is associated with inferior serous retinal detachment. A labeled ultrasound frame indicates the larger temporal lesion and retinal detachment. The OCT scan illustrates a large choroidal mass, marked retinal architecture distortion, and sub-retinal serous edema. The patient initially presented with a lump in the submandibular region and underwent FNA with inconclusive cytology. On re-evaluation and head/neck CT imaging, she was noted to have a submandibular mass and an enlarged lymph node; she subsequently underwent left submandibular gland excision and neck dissection followed by adjuvant chemoradiation. Post-surgical CT of the chest, abdomen, and pelvis revealed multiple small pulmonary lesions bilaterally concerning for metastases. Manifestation of the choroidal lesions was noted on fundus exam approximately two years following the initial diagnosis.
Cai, Qian et al. “Adenoid Cystic Carcinoma of Submandibular Salivary Gland With Late Metastases to Lung and Choroid: A Case Report and Literature Review.” Journal of Oral and Maxillofacial Surgery 72.9 (2014): 1744–1755.
Shie, Jerry A. LDS et al. “Bilateral Choroidal Metastasis From Adenoid Cystic Carcinoma of the Submandibular Gland.” Retina 20.4 (2000): 406–407.
Faculty Approval by: Griffin Jardine, MD; Akbar Shakoor, MD
Author (s): Liang Cheng, 4th Year Medical Student, University of Iowa
Keywords/Main Subjects: Choroideremia
Description of Image:
Choroideremia is a rare X-linked retinal degeneration that typically affects males. It is characterized by progressive degeneration of the retinal pigment epithelium, photoreceptors, and choriocapillaris. In fact, in late stages, the underlying sclera is exposed due to complete chorioretinal dystrophy, hence the name choroid-“eremia” (Greek for bare). The disease is caused by a mutation of the CHM gene, which leads to defects in intracellular vesicular trafficking and subsequent retinal pigment epithelium (RPE), photoreceptor, and choroidal degeneration.
Patients typically present with night blindness and peripheral vision loss in teenage years. Central vision is maintained until the 5th or 6th decade of life but then can rapidly deteriorate. Carriers are mostly unaffected, but there are case reports of symptomatic female patients with less severe features. On dilated fundus exam, the earliest sign is diffuse pigment clumping, followed by atrophy with visible sclera and choroidal vessels. Atrophy progresses centripetally and the fovea is the last to become affected. Choroideremia is usually suspected based on the symptoms and findings, but a full clinical work-up includes a detailed family history, visual field testing, electroretinography (ERG), and genetic testing. Visual field testing shows patchy peripheral vision loss that corresponds to the location of the chorioretinal dystrophy, and ERG shows a reduced scotopic component early on in the disease process. Additional imaging can also be supportive of the diagnosis, such as fundus autofluorescence, infrared (IR) and optical coherence tomography. There are currently no treatments available, but gene therapy trials are underway. The differential to be considered includes retinitis pigmentosa, gyrate atrophy, and ocular albinism.
These color and IR fundus images are of a 35 year old gentleman with an established family history of choroideremia who was diagnosed with the disease in his late 20’s. The color fundus photo of his left eye shows scattered pigment clumping and diffuse atrophy. One can appreciate the bare sclera around the scalloped edge of the remaining healthy retina, as well as the visible large choroidal vessels. The IR fundus photo confirms the retinal atrophy in the periphery with the scalloped border. These findings support patient’s complaints of poor peripheral vision and trouble with night-time driving.
Sorsby A, Franceschetti A, Joseph R, Davey JB. Choroideremia; clinical and genetic aspects. The British journal of ophthalmology. 1952;36(10):547-581.
Huckfeldt RM, Bennett J. Promising first steps in gene therapy for choroideremia. Human gene therapy. 2014;25(2):96-97.
Morgan JI, Han G, Klinman E, et al. High-resolution adaptive optics retinal imaging of cellular structure in choroideremia. Investigative ophthalmology & visual science. 2014;55(10):6381-6397.
Bonilha VL, Trzupek KM, Li Y, et al. Choroideremia: analysis of the retina from a female symptomatic carrier. Ophthalmic genetics. 2008;29(3):99-110.
Faculty Approval by: Dr. Bernstein, Griffin Jardine MD