Central Optic Opacification of a Polymethyl Methacrylate Intraocular Lens Consistent with Snowflake Degeneration
Title: Central Optic Opacification of a Polymethyl Methacrylate Intraocular Lens Consistent with Snowflake Degeneration
Author: Bryan Masino, BS
Photographer: David Chang, MD, Liliana Werner, MD, PhD
Keywords/Main Subjects: Intraocular Lens (IOL), Snowflake Degeneration, Polymethyl Methacrylate (PMMA)
Diagnosis: Three-piece PMMA IOL with clinically significant optic opacity due to snowflake degeneration.
Description of Case: The Polymethyl Methacrylate (PMMA) intraocular lens (IOL) was implanted in the left eye of a 53-year-old female patient in 1985. The lens exhibited slow, yet progressive optic opacification that eventually led to decreased visual acuity. It was therefore explanted on October 13, 2009 (Figure 1), nearly 25 years after the implantation date, by Dr. David Chang from Los Altos, CA. The explanted lens was sent to the Intermountain Ocular Research Center (Mamalis/Werner Laboratory) for further analysis.
Gross examination in the dry state revealed that the optic displayed a prominent white discoloration located within the central 3 mm (Figure 2). Microscopic examination of the dry lens showed multiple lesions with an aspect characteristic of snowflake degeneration (Figure 3).1-3 These lesions were found where the central optic opacity was seen during clinical and gross examinations, and were distributed within the optic substance at different depths. The lesions had the appearance of small spherical “crystals” that were bounded by an outer pseudocapsule suggestively composed of compressed and degenerated PMMA.
The explanted lens was evaluated under anterior segment optical coherent tomography (AS-OCT),4 which showed the abnormal lesions within the optic substance (Figure 4).
As to mimic the environment in which the lens resided while inside of the patients eye, the explanted PMMA IOL was hydrated in balanced salt solution (BSS) and once again analyzed under gross and light microscopy, as well as under the AS-OCT. Upon gross examination the severity of the lens opacification was markedly increased and the diameter thereof nearly doubled to that of approximately 5mm (Figure 5). AS-OCT revealed a much denser and widespread area of snowflake lesions.
The hydrated explant was also evaluated under Scheimpflug photography with densitometry analysis to assess back light scattering.5 This revealed a very high light scattering with a density of 225 CCT at the level of the intraoptical lesions (Figure 7).
Light transmittance was also assessed using a spectrophotometer,5 showing decreased light transmittance through the explanted lens when compared to a control (Figure 8).
The microscopic appearance of the intraoptical lesions is consistent with snowflake degeneration of PMMA material. This is a slowly progressive opacification of PMMA lenses, occurring sometimes 10 years or more after implantation. Snowflake degeneration has been observed in three-piece PMMA lenses implanted between the early 1980’s and the mid 1990’s, which were generally manufactured by injection molding. It has been hypothesized that this degeneration is a result of long-term ultraviolet (UV) exposure. The explanted lenses analyzed in our laboratory had spherical lesions, which were interpreted as foci of degenerated PMMA material clustered in the central zone and midperipheral portion of the optic. This led to the hypothesis that the central optic was exposed to UV light over an extended period, whereas the peripheral optic may be protected by the iris. Therefore, snowflake lesions are generally not observed in the optic periphery. Although the snowflake lesions are dry, it has been observed that an unusual amount of water is collected within the affected optic area upon hydration of explanted PMMA lenses with this condition, leading to more significant optic opacification. Consequently, the clinical significance of snowflake degeneration may depend on the amount of water collected within the IOL optic.3 In vitro studies on three-piece PMMA lenses explanted because of this condition showed that they are associated with a considerable increase in forward light scatter, as well as with a decline of optical quality/performance indicators.6 This can give rise to a variety of subjective complaints, including glare in various illuminating conditions, halos around bright lights, color and contrast loss, as well as hazy vision. These symptoms may prompt IOL explantation even in the absence of significant decrease in visual acuity. It is important to point out that today industry has far greater control over the production of the PMMA material/lenses. Modern PMMA lenses are mostly produced by lathing; therefore, we do not expect to see development of snowflake degeneration in association with them.
Summary of the Case: The patient experienced a decrease in visual acuity due to slow-onset progressive opacification of a PMMA IOL that was implanted over 20 years ago. After the necessary explantation surgery, the lens was examined and exhibited marked snowflake degeneration, which has been observed with three-piece PMMA IOLs that were manufactured during the early 1980’s and the mid 1990’s.
- Werner L. Causes of intraocular lens opacification or discoloration. J Cataract Refract Surg 2007; 33:713-26.
- Apple DJ, Peng Q, Arthur SN, et al. Snowflake degeneration of polymethyl methacrylate posterior chamber intraocular lens optic material: a newly described clinical condition caused by unexpected late opacification of polymethyl methacrylate. Ophthalmology 2002; 109:1666-75.
- Dahle N, Werner L, Fry L, Mamalis N. Localized, central optic snowflake degeneration of a PMMA intraocular lens: Clinical report with pathological correlation. Arch Ophthalmol 2006; 124:1350-3.
- Werner L, Michelson J, Ollerton A, Leishman L, Bodnar Z. Anterior segment optical coherence tomography in the assessment of postoperative intraocular lens optic changes. J Cataract Refract Surg 2012; 38:1077-85.
- Michelson J, Werner L, Ollerton A, Leishman L, Bodnar Z. Light scattering and light transmittance in intraocular lenses explanted because of optic opacification. J Cataract Refract Surg 2012; 38:1476-85.
- Werner L, Stover JC, Schwiegerling J, Das KK. Effects of intraocular lens opacification on light scatter, stray light, and overall optical quality/performance. Invest Ophthalmol Vis Sci 2016; 57(7):3239-47.
Faculty Approval by: Liliana Werner, MD, PhD, and Nick Mamalis, MD.
Disclosure (Financial or other): The author does not have any financial interest in the material and methods mentioned.
Photographic Essay of Idiopathic Intracranial Hypertension-Associated Choroidal Neovascular Membranes
Title: Photographic Essay of Idiopathic Intracranial Hypertension-Associated Choroidal Neovascular Membranes
Authors: Christopher D. Conrady, MD, PhD, Anastasia Neufeld, MD, M.E. Hartnett, MD, Kathleen Digre, MD
Keywords/Main Subjects: Idiopathic intracranial hypertension; Choroidal neovascular membrane; Optic nerve swelling
Secondary CORE Category: Home / Neuro-Ophthalmology / Causes of Decreased Vision
Diagnosis: Choroidal neovascular membrane secondary to chronic optic disc swelling
Description of Case: BG is a 13-year-old, right-handed girl with past medical history of Hashimoto’s thyroiditis who developed acute blurring of the vision in the right eye while reading a book at school. She was seen by outside providers who noted bilateral disc edema and referred her to the emergency department for further evaluation. At time of presentation, she denied pulsatile tinnitus, transient visual obscurations, headache, and diplopia. She denied any new medications but did endorse a 50 lb. weight gain.
On examination, visual acuity was count fingers at 4’ in the right eye and 20/20 in the left. Intraocular pressure was 22 mmHg and 20 mmHg in the right and left eye respectively. There was a small (0.3-0.6 log units), right-sided afferent pupillary defect .Hardy-Rand-Ritter color plates were significantly depressed in the right but not left eye. Flicker fusion was severely depressed at 9 Hz in the right and
normal in the left at 31 Hz. Anterior segment was unremarkable. Dilated eye examination noted significant peripapillary hemorrhages and 360 degrees of edema of the optic nerve in the right eye (Figure 1). The left eye was notable for stage II disc edema.
A Humphrey visual field of the left eye noted an enlarged blind spot, while a Goldman visual field noted a large central scotoma of the right eye (Figure 1c-d). Fluorescein angiography noted a leaking lesion consistent with a peripapillary choroidal neovascular membrane (Figure 2a-c) with fluid extending into the fovea (Figure 2e). B-scan of the globes did not identify optic nerve head drusen (Figure 2d).
The patient was referred to the retina service that performed an intravitreal avastin injection in the right eye. Within a few months, vision returned in the right eye to 20/40 with significant improvement of cecocentral scotoma and resolution of the subretinal fluid (Figure 3a-e).
Figure 1: Acute vision loss in the right eye with bilateral disc edema.
(a-b) Fundus photographs of the left and right eye showed bilateral disc edema. In the right eye (b), there is peripapillary subretinal blood and a choroidal neovascular membrane (yellow arrow). (c) Humphrey visual field noted an enlarged blind spot in the left eye. (d) Goldman visual field noted a central scotoma of the right eye. Left column, left eye; right column, right eye.
Figure 2: Choroidal neovascular membrane with surrounding subretinal fluid and no signs of optic nerve head drusen of the right eye.
(a-c) Fluorescein angiogram of the right eye noted a peripapillary lesion that leaked late consistent with a choroidal neovascular membrane (red arrows). (d) There were no signs of optic nerve head drusen on ultrasound. (e) Macular OCT identified subretinal fluid extending from the optic nerve into the macula (yellow arrow).
Figure 3: Resolution of subretinal fluid with improvement in vision and visual field in the right eye.
(a) Follow up macular OCT of the right eye noted resolution of subretinal fluid in the right eye. Optic disc edema (b-c) and visual fields were also improving in both eyes (d-e). Left column, left eye; right column, right eye.
Summary of the Case:
- Choroidal neovascular membranes can complicate longstanding optic nerve edema in children.
- These membranes respond very well to anti-VEGF therapy.
Faculty Approval by: Dr. Kathleen Digre
Copyright statement: Copyright Conrady, ©2017. For further information regarding the rights to this collection, please visit: http://morancore.utah.edu/terms-of-use/
Title: Birdshot Chorioretinopathy, Case Report
Author: Taylor Fields, Fourth Year Medical Student, Medical College of Georgia
Photographers: Cyrie Fry, CRA, and Paula Morris, CRA.
Secondary CORE Category: Retina and Vitreous / Focal and Diffuse Choroidal and Retinal Inflammation
Keywords/Main Subject: Posterior Uveitis; Chorioretinopathy; Birdshot; BSCR; BCR Diagnosis- Birdshot Chorioretinopathy
Brief Description of Case:
This case is a 52-year-old white female who presented complaining of “hundreds of floaters” that had been progressing for several months in both eyes. She noted a crescent shape to the floaters and a one month of a small blurry spot in the inferonasal visual field in her right eye. She also described nyctalopia, a less vivid quality to her vision and morning photopsias and black spots upon awakening that lasted about 30 minutes.
Visual acuity was 20/20 in each eye and intraocular pressure by tonopen was 21 and 19 in the right and left eyes respectively. Her pupillary exam, visual fields, color vision and motility were all normal. The Fundus exam revealed 1+ disc edema, bilateral epiretinal membranes, narrowing of her retinal vessels and numerous mid-peripheral white/yellow choroidal spots bilaterally (Pictures 1-4). ICG photos revealed areas of decreased dye perfusion within the choroid (Picture 3).
The differential diagnosis included inflammatory uveitis (birdshot chorioretinopathy, sarcoidosis), infectious causes (TB, syphilis, Lyme disease) and masquerade syndromes such as choroidal lymphoma. She was found to be HLA-A29 positive. An extensive laboratory work-up was otherwise negative. Full-field electroretinograms (ffERGs) showed attenuated scotopic dim blue flash ERGs to about 59% with slowed photopic b-wave time of 35 milliseconds.
The patient was diagnosed with birdshot chorioretinopathy (BSCR). Her fundus exam and ffERG results are typical of early stages of BSCR. This disease is an idiopathic posterior uveitis that commonly presents in Caucasians in their sixth decade of life. It has a strong association with the human leukocyte antigen HLA-A29 (96% of patients are carriers).1,2 BSCR typically presents with a gradual centripetal loss of vision and presence of floaters.3
The patient was started on a 60 mg prednisone taper as well as mycophenolate and cyclosporine. Systemic immunomodulatory therapy is the mainstay of treatment for BSCR. Concomitant therapy with an antimetabolite and a T-cell inhibitor can be beneficial for preserving vision, and decreasing the cumulative glucocorticoid dose.4,5
BSCR is considered a chronic and progressive isolated ocular disorder. A majority of patients develop retinal dysfunction; however, central vision is typically spared until late in the disease. Visual acuity at initial presentation is a prognostic factor for long-term visual outcomes with appropriate treatment.6
Picture 1. Full color montage photos of the right (A) and left (B) eyes. These show characteristic pisiform lesions of BSCR within the periphery of the retina (black arrows).
Picture 2. These are color (A & C) and red free (B & D) photos of the left (A & B) and right (C & D) fundi. The periphery has areas of white/yellow choroidal spots (black arrows). There is also narrowing of vessels and disc edema present.
Picture 3. These are late ICG photos of the nasal portions of the Left (A) and Right (B) retinas. There is decreased choroidal perfusion, and thus dark spots, in the areas of inflammation (black arrows).
Picture 4. These are wide field fluorescein angiograms (FA) of the right (A) and left (B) fundi. This shows vasculature leakage, periphlebitis, and disc edema.
Summary of Case
This is a 52 year-old white female diagnosed with birdshot chorioretinopathy who presented with several months of worsening floaters and was found to have the characteristic midperipheral white/yellow choroidal lesions bilaterally. She was found to be HLA-A29 positive, confirmatory of the diagnosis.
Levinson RD, Brezin A, Rothova A, et al. Research criteria for the diagnosis of birdshot chorioretinopathy: results of an international consensus Am J Ophthalmol 2006; 141:185 – 187.
- Brézin AP, Monnet D, Cohen JH, Levinson HLA-A29 and birdshot chorioretinopathy.Ocul Immunol Inflamm. 2011;19(6):397-400.
- Shah KH, Levinson RD, Yu F, et al. Birdshot chorioretinopathy. Surv Ophthalmol 2005; 50:519 –
- Becker MD, Wertheim MS, Smith JR, Rosenbaum Long-term follow-up of patients with birdshot retinochoroidopathy treated with systemic immunosuppression. Ocul Immunol Inflamm 2005; 13:289–293.st
- Kiss, Szilard, Ahmed, Muna, Letko, Erik, & Foster, Stephen. (2005). Long-term Follow- up of Patients with Birdshot Retinochoroidopathy Treated with Corticosteroid-Sparing Systemic Immunomodulatory Therapy. Ophthalmology, 112(6), 1066-1071.e2.
- Tomkins-Netzer O, Taylor SR, Lightman Long-term clinical and anatomic outcome of birdshot chorioretinopathy. JAMA Ophthalmol 2014; 132:57 – 62.
Faculty Approval by: Griffin Jardine, MD
Title: Opthalmoplegic Migraine/Recurrent Painful Ophthalmoplegic Neuropathy
Author Information: Ryan O’Meilia MS4, University of Oklahoma; Judith Warner MD, John A. Moran Eye Center
Financial Disclosure: None
Date: September 2015
Keywords: Opthalmoplegic Migraine; Recurrent Painful Ophthalmoplegic neuropathy
Chief Complaint: Lid drooping and drifting eye
History of Present Illness:
This case discusses a 3 year old girl with a symptomatic, recurring oculomotor palsy. Her first episode was at age one but completely resolved. Four days prior to her most recent presentation she had a gastroenteritis with vomiting and decreased energy. Her parents did not note a fever, upper respiratory infection, cough, eye pain, rash or HA in the past few weeks. The gastroenteritis resolved two days later but around that same time she developed right ptosis. Over the next two days the eyelid drooping progressed and the patient developed deviated eye and asymmetric pupils.
Her previous episode of oculomotor nerve palsy developed much like the present one. The parents report a sub-acute onset over a few days that progressed from ptosis, to anisocoria and strabismus. The episode resolved without treatment over about one week. An MRI was performed at an outside hospital and the read was as follows: “Enhancement of the right third cranial nerve (CN) which is most prominent immediately adjacent to the origin of the nerve at the brain stem. The enhancement extends anteriorly along the nerve to the cavernous sinus.” Her clinical presentation and imaging were felt to be consistent with inflammatory neuritis, most likely post viral.
Past Medical History: otherwise non-contributory
Past Surgical History: None
Allergies: No known drug allergies
Immunizations: Up to date
Development: Age appropriate
Family History: No family history of eye disease, migraine, MS, neurologic disease, childhood cancers. Maternal cousins with celiac disease and DM1
Social History: Lives with parents; 2 cats and a dog. Attends daycare
Review of Symptoms: All negative except as above
Ocular Physical Exam:
- General: Alert and oriented, NAD
- Visual Acuity: Fix and Follow OU
- OD: 5mm > 4mm
- OS: 4mm > 2mm
- Primary gaze: right eye deviated inferiorly and temporally
- -3 adduction
- -2 elevation
- -1 depression
- -0 abduction
- Full EOM
- Orbits: No deformities, ecchymosis or edema
- Lids/Lashes: Right ptosis, MRD1 5mm, normal eyelid position OS
- Conjunctiva/Sclera: white and quiet OU
- Cornea: clear OU
- Anterior Chamber: formed without hyphema or hypopyon OU
- Iris: flat and round OU
- Lens: WNL OU
- Dilated Fundus exam:
- Optic Nerve: sharp margins, no disc edema
- Macula: Healthy OU
- Vessels: Normal caliber OU
- Periphery: WNL OU
Vital signs and labs:
- Sat: 99% RA
- CRP, BMP CBC: within normal limits
- Post-Viral Neuritis
- Ophthalmoplegic migraine/Recurrent painful ophthalmoplegic neuropathy (OM/RPON)
- Miller-Fisher Syndrome
- TB, Lyme, Sarcoid, Lymphoma
Based on clinical presentation, the list of differential diagnoses for our patient’s third nerve palsy would be quite extensive. ADEM and Miller-Fischer syndrome can present as third nerve palsies but they would also tend to be accompanied by other neurologic deficits such as ataxia or areflexia. When the recurrent and resolving history is taken into account aneurysm, schwannoma, TB, Lyme, sarcoid, and lymphoma become less likely as these would tend to be slowly progressive and unlikely to resolve without treatment. Imaging confirms the absence of schwannoma and also rules out Tolosa-hunt which would show inflammation in the cavernous sinus and meningeal enhancement. Aneurysm, Tolosa-Hunt, and Miller-Fisher syndrome would also be quite rare in this age group.
With all of these factors taken together the most likely diagnosis is either post-viral neuritis or Ophthalmoplegic migraine/Recurrent painful ophthalmoplegic neuropathy (OM/RPON). It is possible that these two conditions are related.
OM/RPON is a rare condition with a prevalence of 0.7 per million6; it usually begins in childhood.2,3 A systematic review authored by Gelfand found a median age of onset at 8 years old (interquartile range 3, 16). They also found that approximately 2/3 of patients affected by OM/RPON were female. 4
Signs and Symptoms
OM/RPON typically presents as a headache followed by ophthalmoplegia. If aheadache is present, it is typically unilateral and ipsilateral to the affected eye. The headache may or may not have migrainous features: photophobia, phonophobia, or nausea/vomiting. The ophthalmoplegia can occur immediately or up to 14 days after the headache. One or multiple nerves may be also be involved. The frequency of nerves affected in Gelfand’s paper was CN III 83%, CNVI 20%, and CNIV 2%. If multiple nerves were affected, CNIII was always included.4 When CNIII is affected it may be a partial or complete palsy. Both ptosis and mydriasis are common, especially among children.
The diagnostic criteria have according to the International Classification of Headache Disorder 3-beta1 are:
- At least two attacks fulfilling criterion
- Unilateral headache accompanied by ipsilateral paresis of one, two or all three ocular motor
- Orbital, parasellar, or posterior fossa lesion has been excluded by appropriate
- Not better accounted for by another ICHD-3 diagnosis
As stated above, before the diagnosis of OM/RPON is made it is critically important to rule out other possible etiologies such as aneurysm, schwannoma, granulomatous disease, and inflammatory neuropathy.2
The pathophysiology of OM/RPON is a topic of ongoing debate. The diagnostic criteria in ICHD have been updated over the years to mirror the trends in the etiologic discussion by classifying it first as a migraine, then as a neuralgia, and most recently as a neuropathy.5 In fact, with the newest release of ICHD-3beta, the International Headache Society recommended the term ‘ophthalmoplegic migraine’ be abandoned.1 The driving force for this progression has been the need to explain the reversible contrast enhancement at the root entry zone of the affected cranial nerve.
Some who support the viewpoint of a neuropathy will point to the possibility of a benign neurotropic viral infection and highlight the similarities of the imaging in OM/RPON to those found in Bell’s Palsy.2 Others advocate for an immune-mediated neuropathy similar to chronic inflammatory demyelinating polyneuropathy (CIDP).5 In both of these explanations, the headache of OM/RPON is a result of inflammation of the nerve. The inflammation causes vasoconstriction of the nearby vasculature subsequently triggering the headache. However, these hypotheses are not without their weaknesses, CSF analysis and viral studies typically return unremarkable in OM/RPON.
Even with the current trend towards viewing OM/RPON as a neuropathy, there are still some who continue to advocate for a migrainous etiology. A paper published in 2014 proposed that a migraine induced vasospasm of the arteries supplying CNIII, IV, or VI could lead to ischemia of the nerves causing reversible breakdown of the nerve-blood barrier allowing for contrast extravasation and subsequent nerve enhancement on MRI.3 The authors make a great case, yet still leave questions unanswered. If migraine is the causal process then why does treatment with acute and prophylactic migraine medication offer little to no benefit or protection to patients?
In summary, there is still much work to be done towards reaching an understanding of how and why OM/RPON occurs. It is valuable to consider that OM/RPON may in fact have a multifactorial etiology resulting from processes and predispositions related to both neuropathy and migraine.
With such ambiguity clouding the pathophysiology of OM/RPON it follows that there is also uncertainty regarding effective treatment for the condition.
Migraine medications both acute and prophylactic have been tried with unconvincing efficacy while the results of steroids have been positive yet mixed. Gelfand found steroids to be beneficial in 54% of cases reviewed. Yet the effects were either unclear, not beneficial or even harmful in 35%, 8%, and 4% respectively.4
Prognosis in OM/RPON is generally excellent and most patients can experience a full recovery in days to weeks. However small minority of patients may be left with persistent neurological deficits, especially those who suffer from repeated attacks.2,3,4,5
Faculty Approval by: Griffin Jardine, MD
- The International Classification of Headache Disorders, 3rd edition (beta version).
- Alexander, Al. Ophthalmoplegic Migraine: Reversible Enhancement and Thickening of the Cisternal Segment of the Oculomotor Nerve on Contrast-Enhanced MR Images. AJNR Am J Neuroradiol 19:1887–1891, November 1998
- Ambrosetto, Al. Ophthalmoplegic migraine: From questions to answers. Cephalalgia 2014, Vol. 34(11) 914–919
- Gelfand, Al. Ophthalmoplegic ‘‘Migraine’’ or Recurrent Ophthalmoplegic Cranial Neuropathy: New Cases and a Systematic Review. Journal of Child Neurology 27(6) 759-766. 2012
- Fö rderreuther, From Ophthalmoplegic Migraine to Cranial Neuropathy. Curr Pain Headache Rep (2015) 19: 21 DOI 10.1007/s11916-015-0492-1
- Quisling, Ophthalmoplegic Migraine: 30-year-old male with migraine headaches and occasional diplopia. http://webeye.ophth.uiowa.edu/eyeforum/cases/52-Ophthalmoplegic- Migraine-Diplopia-Headache.htm
Title: Retinal Vasculitis Case Report
Author: Sherief Raouf, Visiting Medical Student from the Stony Brook School of Medicine
Photographer: Glen Jenkins
Date: Friday, August 19, 2016
Diagnosis: Idiopathic mixed arterial/venous occlusive vasculitis
Secondary CORE Category: Retina and Vitreous / Focal and Diffuse Choroidal and Retinal Inflammation
Description of Image:
|Negative Laboratory Workup|
|ANCA||Systemic necrotizing vasculitis|
|Serine Proteinase Ab||Systemic vasculitis|
|HbSAg, HbSAb||Hep B|
|ANA||Sensitive for SLE|
|Anti-Smith Ab||Specific for SLE|
|dsDNA Ab||Lupus Nephritis & SLE|
|Rh Factor||Rheumatoid Arthritis|
|Cardiolipin Ab and B2GP Ab||Anti-phospholipid syndrome|
|SSA Ab and SSB Ab||Sjogren’s & SLE|
|Ribonucleic Protein Ab||SLE & Mixed connective tissue disease|
|PT, PTT, dRVVT||Hypercoagulability|
Background: The patient is a 52 year old woman with a past medical history of diabetes mellitus and hypothyroidism who presented complaining of reduced vision OD, described as a “large grey spot in the center.” Visual acuity was 20/30 OD, 20/20 OS, pupils equal and reactive to light with no afferent pupillary defect, and the anterior chamber deep and quiet OU. The vitreous OD demonstrated +1 cells and the macula OD exhibited pigmentary atrophy and a small superior branch retinal artery occlusion (BRAO), while both eyes showed signs of periphlebitis.
There were no obvious signs of systemic inflammatory disease including Lupus, Sjogren’s, Giant-cell Arteritis, Granulomatosis with polyangiitis, or other systemic vasculitis. The review of systems was negative for cough, fever, orogenital ulcerations (Behçet disease), hearing loss and encephalopathy (Susac syndrome), or skin rash. Initial laboratory workup is shown in Table 1.
A laboratory investigation of infectious causes was performed and the following tests were negative: quantiferon, FTA-ABS, RPR, B. Burgdorferi Ab, toxoplasmosis and HIV ELISA. A laboratory workup for hypercoagulability was also negative (including PT, PTT, dRVVT). Brain MRI was negative for any acute intracranial process or findings of vascular inflammation or stenosis. Chest X-ray showed normal vascular markings, and a lack of any nodules, consolidations or hilar adenopathy.
The diagnosis of an arterial occlusive vasculitis was made, and treatment with oral Prednisolone and Mycophenolate mofetil was begun. One month later, the patient returned complaining of worsening blurriness OD. Exam revealed decreased vitreous cells with a persistent superior BRAO, periphlebitis and retinal neovascularization OD. The decision to treat the right eye with peripheral panretinal photocoagulation (PRP) was made. Over the ensuing months, the retinal vasculitis was medically managed with courses of prednisolone, mycophenolate and methotrexate and regular follow-up maintained. The photos above are taken from a visit 12 months after the initial visit, upon which a new BRAO was discovered.
The fundus photo demonstrates the gray-white sheathing of a retinal branch artery that is characteristic of a retinal vasculitis.1 The perivascular sheathing in occlusive vasculitis is thought to be an exudate of inflammatory cells around the vessel that leads to occlusion (Figure A, yellow arrow). Occlusion of the retinal vessel can result in ischemia of the retina and areas of capillary non-perfusion. This fundus photo demonstrates such an area of ischemic retina that is seen downstream and superior to the occluded vessel. This retina also exhibits neovascularization coincident with the ischemic areas of retina.
The late frame fluorescein angiography shows evidence of vascular obstruction in the inferior arcade, distal to the sheathed retinal branch artery. There is evidence of diffuse retinal vasculitis and vessel leakage. In addition, we can see the area of prior PRP of the areas of retinal capillary non-perfusion (Figure B, blue arrow). The angiography is able to additionally define the zones where the loss of retinal perfusion (Figure A, white arrow) has led to new areas of leaking neovascularization. Notably, there is a pronounced macular hyperfluorescence that corresponds to neovascularization (Figure B, green arrow). Given that neovascularization has continued, and that the vasculitis is active, the decision to restart corticosteroid treatment was undertaken with a plan for another round of PRP. Typically it would be preferable to ensure that the vasculitis is inactive when PRP is implemented, as its use can result in the release of more angiogenic factors, aggravating neovascularization.2
A key distinction to be made in making this diagnosis is between that of primary branch retinal vein occlusions, which closely mimics idiopathic retinal vasculitis. In BRVO, the occlusions typically occur at arteriovenous crossings, and are not multiple nor as peripheral as they tend to be in vasculitic obstructions.3 Finally, it should be said that there is some consensus to label idiopathic retinal vasculitis as Eales disease when vascular occlusions and neovascularization lead to recurrent vitreous hemorrhage in the presence of serological evidence of tuberculosis.3 Admittedly, this distinction may be a semantic one, as the yet unsolved pathophysiology may one day reveal these two entities to lie on one spectrum.
The differential for retinal vasculature occlusions is very broad and can be usefully divided into non-inflammatory (Diabetes, BRVO) and inflammatory causes. Inflammatory etiologies were examined with a careful history and an extensive laboratory and radiologic workup, yielding no clear cause. Indeed, many inflammatory retinal vascular obstructions are secondary to a systemic inflammatory process (infectious and non-infectious). However, primary idiopathic retinal vasculitis often is isolated to the eye and absent of any systemic involvement, frequently making this a diagnosis of exclusion.4
Format: Fundus photography and fluorescein angiography
- Gass, J. Donald M. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment. St. Louis: Mosby, 1997. Print.
- Biswas, J. et al. Eales disease–an update. Surv Ophthalmol 47, 197–214 (2002).
- Namperumalsamy, P., and Dhananjay S. “Eales ” Retina. Stephen Ryan MD et al. 5th ed. Oxford: Saunders, 2013. 1479-1485. Print.
- Saurabh, K., Das, R., Biswas, J. & Kumar, A. Profile of retinal vasculitis in a tertiary eye care center in Eastern India. Indian Journal of Ophthalmology 59, 297 (2011).
Faculty Approval By: Dr. Akbar Shakoor, Dr. Griffin Jardine
Disclosure: No financial disclosures to share
Title: Fundus Photography and Fluorescein Angiography of Familial Exudative Vitreoretinopathy
Author: Kenneth Price, BS
Image or video:
Keywords/Main Subjects: Familial Exudative Vitreoretinopathy; FEVR
Diagnosis: Familial Exudative Vitreoretinopathy
Description of Image: Familial Exudative Vitreoretinopathy (FEVR) is a rare inherited disorder of retinal blood vessel development which leads to incomplete vascularization of the peripheral retina. Inheritance can be autosomal dominant, recessive, X-linked, or sporadic. The disease ranges from asymptomatic to severe. If there is sufficient retinal ischemia secondary vascular proliferation can lead to fibrosis, traction, retinal detachment and retinal dysplasia. FEVR needs to be distinguished from ROP due to their similar appearances. The diagnosis of FEVR is made in patients who were born at full term or otherwise have findings inconsistent with ROP and can further be ruled in by genetic testing, specifically testing for FZD4, LRP5, TSPAN12, NDP and FZ mutations among others. Many patients diagnosed with FEVR retain vision of 20/40 or better. Macular ectopia, retinal folds, and retinal detachments are the main causes for visual loss. A fundamental component of diagnosis and treatment is identifying peripheral retinal areas of non-perfusion by performing fluorescein angiography, often under anesthesia due to this disease most commonly presenting in the pediatric age range. Wide-field angiography has become particularly useful in this disease.
This fundus photo and fluorescein angiography photo are from a 4 year old female who was diagnosed with FEVR at an early age after her parents began to notice symptoms of vision loss. On exam, she was found to have an avascular retina peripherally and was followed until she developed neovascularization and associated fibrosis. Fundus photography and fluorescein angiography here show a broad linear macular fold with associated epiretinal membrane and peripheral avascular retina with areas of photocoagulation. She was treated with peripheral photocoagulation, vitrectomies to release vitreoretinal traction, and a scleral buckle for retinal detachment.
Gilmour DF. Familial exudative vitreoretinopathy and related retinopathies. Eye (2015) 29, 1–14.
John VJ, McClintic JI, Hess DJ, Berrocal AM. Retinopathy of Prematurity Versus Familial Exudative Vitreoretinopathy: Report on Clinical and Angiographic Findings. Ophthalmic Surg Lasers Imaging Retina. 2016 Jan;47(1):14-9.
Faculty Approval by: M.E. Hartnett; Griffin Jardine
Disclosure (Financial or other): None
Title: Stargardt disease
Author (s): Jamie Odden, MS4 MPH
Image or video:
Keywords/Main Subjects: Stargardt Disease; Central macular atrophy; Inherited macular dystrophy
Diagnosis: Stargardt Disease
Description of Image:
Epidemiology: Stargardt disease is the most common inherited macular dystrophy, with a prevalence of approximately 1 in 8,000-10,000 individuals. It is a common cause of central vision loss in individuals under 50 years old, with typical onset between 10-20 years old.
Genetics: The underlying etiology is due to accumulation of lipofuscin in the retinal pigment epithelium (RPE). Most cases are autosomal recessive due to mutations in the ABCA4 gene, which encodes for a transporter protein expressed by rod outer segments. ABCA4 mutations can cause toxins to accumulate in the photoreceptors, leading to formation of lipofuscin. Fewer cases are autosomal dominant due to a mutation in ELOVL4, which encodes a component of the fatty acid elongation system in photoreceptors.
Clinical exam: Classic fundoscopic findings include “beaten bronze” central macular atrophy surrounded by yellow round or pisciform flecks (Figure 1). The condition is referred to as “fundus flavimaculatus” if the discrete yellow flecks are widespread throughout the fundus retinal pigment epithelium (RPE). “Fundus flavimaculatus” is a milder condition rendering better visual function due to less macula involvement.
Diagnosis/testing: Fundus autofluorescence (FAF) and optical coherence tomography (OCT) can confirm diagnosis and help stage the disease. FAF and OCT often detect RPE changes before they are found on clinical fundoscopic exam. Commonly, FAF shows a hypofluorescent macula, corresponding to atrophy, and surrounding hyperfluorescent spots, corresponding to lipofuscin deposits in the RPE (Figure 2).
OCT demonstrates thinning and disorganization of the inner segment-outer segment (IS-OS) junction of the photoreceptors in the macula (Figure 3). Total loss of the IS-OS is possible over time. Choroidal hyper-reflectivity often occurs due to overlying retinal atrophy.
Historically, the “dark choroid sign” on fluorescein angiography (FA) was used to confirm clinical diagnosis, though FA has been largely replaced by FAF and OCT. The sign is present in over 80% of patients. Evidence suggests that the sign is caused by accumulation of lipofuscin throughout the RPE which masks background choroidal fluorescence.
Clinical course: In most cases, central vision loss is slow and progressive. Later-onset disease is associated with a better prognosis. Visual acuity ranges from 20/50 to 20/200, with most individuals maintaining fair acuity in one eye.
Management: Stargardt disease is incurable. No treatments are available to slow progression, though pharmacologic and genetic therapies are under investigation. Individuals should avoid vitamin A supplementation and minimize exposure to bright sunlight. Additionally, low vision therapy should be considered.
- North V, Gelman R, Tsang SH. Juvenile-Onset Macular Degeneration and Allied Disorders. Developments in ophthalmology. 2014;53:44-52. doi:10.1159/000357293.
- Liu A, Lin Y, Terry R, Nelson K, Bernstein PS. Role of long-chain and very-long-chain polyunsaturated fatty acids in macular degenerations and dystrophies. Clin Lipidol. 2011;6(5):593-613.
- Regillo C, ed. Basic and clinical science course (BCSC) 2012-2013: Retina and vitreous section 12. San Francisco, United States: American Academy of Ophthalmology; 2012.
Faculty Approval by: Paul Bernstein, MD PhD; Griffin Jardine, MD
Disclosure (Financial or other): None
Title: Primary Acquired Melanosis (PAM) with Atypia: Pathology and Clinical Correlations
Author (s): Jack Li, BA
- Pathology Photomicrographs: Jack Li
- Clinical Photo: Dr. Amy Lin
Keywords/Main Subjects: Primary Acquired Melanosis, Melanocytic Lesions of Ocular
Diagnosis: Primary Acquired Melanosis with Atypia
Description of Images:
Primary acquired melanosis (PAM) of the conjunctiva is a pigmented lesion of the conjunctiva that is flat, painless and non-cystic. PAM typically occurs unilaterally, is more likely to occur in lightly pigmented individuals and is most likely to present in the 6th decade of life. PAM represents 11% of all conjunctival tumors and 21% of all conjunctival melanocytic lesions1. Figure A is the external photography of a 60-year-old female with approximately 13-year history of PAM of the conjunctiva. Features associated with PAM include unilaterality, waxing and waning of size and pigment over time and a mottled or dusted pigmented appearance. PAM most commonly occurs on the bulbar conjunctiva, limbal conjunctiva and cornea. The typical patient is a Caucasian adult presenting around 60 years of age. PAM is divided histopathologically into PAM with or without atypia. PAM with atypia has a high chance of progression into melanoma while PAM without atypia has little chance of progressing to melanoma2. Biopsy and histopathologic examination allow determination of the presence or absence of atypia. Because PAM with atypia has significant risk of progression into melanoma, a potentially lethal tumor, surgical and medical intervention is warranted. Figure B represents the same patient after excision of the lesion and cryotherapy.
PAM without atypia is defined as pigmentation of the conjunctival epithelium with or without benign melanocytic hyperplasia. PAM with atypia is characterized by the presence of atypical melanocytic hyperplasia. Mild atypia is defined as atypical melanocytes confined to the basal layer of the epithelium; severe atypia is defined as atypical melanocytes that extend into the superficial non-basal portion of the epithelium and may contain epitheloid cells1. Figure C and D are low and medium H&E photomicrographs of the specimen obtained from the patient where pigmentation along the basal layer of the epithelium can be appreciated. One can appreciate the extension of atypical melanocytes mid-way into the epithelium, qualifying this lesion to be PAM with severe atypia.
Atypia is determined by cytological features and growth patterns that are associated with malignant potential. Four types of atypical melanocytes include the small polyhedral cells, epitheloid cells, dendritic cells, and spindle cells. Polyhedral cells contain small, round nuclei with little cytoplasm. Epitheloid cells contain abundant eosinophilic cytoplasm. Spindle cells are aligned such that the long axis are parallel to the basement membrane. Dendritic cells are large cells with complex branching dendrites found along the basilar layer3.
The mainstay of treatment of PAM with atypia is wide excision of the lesion and cryotherapy of the borders of the lesions. Amniotic graft can be applied to the surgical site to facilitate healing. Topical chemotherapy, most commonly with mitomycin-c, can be used as adjuvant therapy in cases of diffuse lesion, positive surgical margins, large lesions that cannot be completely removed, or in cases of recurrent disease2. Interferon a-2b has shown promise as a medical management. A six-week trial showed that successive application of interferon a-2b resulted in shrinking of PAM4.
- Shields, J. A. et al. Primary acquired melanosis of the conjunctiva: experience with 311 eyes. Trans. Am. Ophthalmol. Soc. 105, 61-71–2 (2007).
- Oellers, P. & Karp, C. L. Management of pigmented conjunctival lesions. Ocul. Surf. 10, 251–263 (2012).
- Folberg, R., McLean, I. & Zimmerman, L. Primary acquired melanosis of the conjunctiva. Hum. Pathol. 16, 129–35 (1985).
- Garip, A. et al. Evaluation of a short-term topical interferon α-2b treatment for histologically proven melanoma and primary acquired melanosis with atypia. Orbit 35, 29–34 (2016).
Faculty Approval by: Amy Lin, MD; Griffin Jardine, MD
Disclosure (Financial or other): None
Title: Parry-Romberg Syndrome Case Report
Author: Rebekah Gensure, PhD, 4th Year Medical Student, Rutgers Robert Wood Johnson Medical School; Laura Hanson, MD, Neuro-Ophthalmology Fellow, John A. Moran Eye Center; Kathleen Digre, MD, John A. Moran Eye Center
Photographer: James Gilman
Date: July 20, 2015
Moran CORE: Orbits, Eyelids, and Lacrimal System/Periocular Malpositions and Involutional Changes/Involutional Periorbital Changes
Keywords/Main Subjects: Parry-Romberg Syndrome, hemifacial atrophy
Diagnosis/Differential Diagnosis: Parry-Romberg Syndrome, post traumatic fat atrophy, hemifacial microsomia (first and second branchial arch syndrome), Goldenhar’s syndrome
Brief Description of Case:
A 27-year-old female patient presented with a long history of facial asymmetry and right tongue atrophy. She was diagnosed with Parry-Romberg syndrome 7 years ago, at the age of 20. At the time of her initial diagnosis at an outside institution, the patient report experiencing significant facial pain and wasted facial appearance that had been present for many years and had gone undiagnosed until that point. Presently, the patient is status-post surgical repair (hemifacial fat grafting) with a satisfactory cosmetic result.
The patient also has a history of migraine headache. At the time of the most recent visit, the patient reported improvement in migraine headaches with no preventative medications currently. Headaches have been less frequent (approximately 1 every 2 weeks) and pain rating no worse than 5/10. She also reports episodic ptosis, which appears to be related to migraine and menstrual cycle.
Other ocular history includes a history of treated amblyopia secondary to accommodative esotropia and is still in spectacle correction.
Best corrected visual acuities: 20/20 OD and 20/20 OS.
Pupils: 3mm OU light, 7 mm OU dark; briskly reactive OU with no RAPD EOM: -½ OD on right gaze; Orthotropic at distance; exophoria at near Exophthalmometry: 13 mm OD, 16 mm OS
Color Vision: 10/10 OU Ishihara
Stereo Vision: +Fly, 3/3 animals, 7/9 circles IOP: 16 mm Hg OD & OS.
VF: Full OU
SLE: Anterior segment within normal limits
Fundus: Within normal limits; C/D ratio 0.1 OD, 0.2 OS Refraction: OD +2.50 sphere, +0.75 cylinder at axis 25
OS +1.50 sphere, +1.50 cylinder at axis 130
NEURO: Completely normal neurological examination except for the facial asymmetry.
Hemifacial atrophy, also known as Parry-Romberg syndrome, is characterized by a slow progressive deterioration (atrophy) of the skin and subcutaneous tissue structures on half of the face . As it is described by Parry, Henoch and Romberg in the early 19th century, there is wasting of the subcutaneous fat with or without atrophy of adjacent skin, bone, and cartilage [2- 3]. The condition is typically insidious in onset, and progression is variable. In some cases, atrophy may halt before the entire hemi-face is involved but with residual disability . In mild cases, there may be only minor cosmetic effects without any disability.
Because of the relative rarity of this condition, associated clinical conditions have mostly been identified through case reports. For example, in 1985, Sagild and Alving reported a case associating hemiplegic migraine with hemifacial atrophy . Seizures are also commonly reported to co-occur with hemifacial atrophy, particularly contralateral simple partial or generalized seizures . Additionally, Parry-Romberg syndrome has sometimes been associated with localized scleroderma, although this association remains controversial.
Long-term progression of the condition has not been well documented; however, one interesting case report followed several patients over time, including one patient who was followed for over 43 years . For this particular long-term follow-up patient, progression of facial atrophy appeared to progress until age 15 but then slow or stop until age 23, at which point new onset hyperreflexia of the contralateral lower extremity was noted. Over the years, the facial atrophy remained apparently stable, although his neurological function gradually declined; by age 58, he demonstrated wide-based gait with absent plantar and tendon reflexes, mildly diminished pain and temperature sensation, end-position nystagmus, and difficulty with heel-to-shin and tandem testing.
Treatment options are limited for patients diagnosed with Parry-Romberg hemifacial atrophy. Currently, there are no known therapies that will stop progression of the disease.
Reconstruction has been utilized, with variable results depending on the timing of the intervention. For the best results possible, timing of surgery should be strategized according to when the disease appears to have exhausted its course and facial growth is completed .
Images or Video:
Summary of the Case:
The patient is a 27-year-old woman with Parry-Romberg syndrome with hemifacial atrophy, status-post reconstructive surgical repair with a satisfactory cosmetic result. Overall, the patient is quite stable, with no major new changes in facial structure visible on external exam as compared to prior exams. Based on the apparent stability of the disease process and satisfaction of the patient with her appearance, the patient was recommended to return to clinic only for yearly follow-up or sooner as needed.
- Esan T and Olusile Hemifacial Atrophy: A Case Report And Review Of Literature. The Internet Journal of Dental Science. 2003. 1(1).
- Parry Collections from the unpublished medical writings of the late Caleb Hillier Parry, M.D., F.R.S. 1825 London: Underwoods. 478–80.
- Romberg, MH; Henoch, EH (1846). Krankheiten des nervensystems (IV: Trophoneurosen). Klinische ergebnisse (in German). Berlin: Albert Förstner. 75–81.
- NINDS Parry-Romberg Information Page [Internet]. Bethesda: Office of Communications and Public Liaison, National Institute of Neurological Disorders and Stroke, National Institutes of Health; January 25, Available from: http://www.ninds.nih.gov/disorders/parry_romberg/parry_romberg.htm
- Sagild JC and Alving Hemiplegic migraine and progressive hemifacial atrophy; June 1985; 17(6): 620.
- Wolf SM and Verity Neurological complications of progressive facial hemiatrophy. J Neurol Neurosurg Psychiatry. 1974 Sep; 37(9): 997–1004.
- Asher SW and Berg Progressive hemifacial atrophy: Report of three cases, including one observed over 43 years, and computed tomography findings. Arch Neurol. 1982; 39: 44-46.
Faculty Reviewer: Griffin Jardine, MD
Title: Band Keratopathy Case Report
Author: Martin de la Presa, BA
Keywords / Main Subjects: Band keratopathy; calcium hydroxyapatite deposition
Diagnosis / Differential Diagnosis: Interstitial keratitis; calcareous degeneration; calciphylaxis
Brief Description of Image: Band keratopathy is the pathological deposition of calcium within the superficial layers of the cornea, specifically Bowman’s layer. The condition ranges from asymptomatic to causing ocular irritation, foreign body sensation and decreased vision. Though it is often idiopathic there is a broad differential of local and systemic associated diseases. The local causes include chronic ocular irritation or inflammatory conditions such as chronic anterior uveitis (especially in Juvenile Idiopathic Arthritis), interstitial keratitis, superficial keratitis, phthisis bulbi, end-stage glaucoma and silicone oil left in the aphakic eye. Systemic diseases associations include those diseases that elevate serum calcium levels such as in hyperparathyroidism, sarcoidosis, multiple myeloma, hypophosphatemia, Paget disease and chronic renal failure.
On exam, there is a white band-like formation of calcium across the corneal surface with irregular boarders and a peripheral clearing of cornea between the calcium deposits and the limbus. The calcium deposition is typically found beneath the epithelial layer within Bowman’s layer but may extend into anterior stroma. In the absence of an explainable local etiology laboratory testing is recommended to assess serum calcium and phosphate levels and renal function. When symptomatic, the calcium deposits can be removed with superficial debridement and manual scraping of the corneal surface with or without the aid of a chelating agent such as ethylenediaminetetraacetic acid (EDTA). Recurrence is common unless the predisposing cause is identified and treated.
Faculty Approval: Griffin Jardine, MD