A New Rapidly Growing Dome-Shaped Choroidal Lesion in an Eye with Treated Retinoblastoma.

BACKGROUND: To describe an extensive untreatable choroidal metastasis by retinoblastoma in the treated patient which was clinically indistinguishable from regular tumor recurrence. METHODS: A 24-month-old girl without a family history of retinoblastoma (RB) was discovered to have group C RB in her right eye and group D in her left eye. The patient received 12 cycles of intravenous chemotherapy, intra-arterial chemotherapy (IAC), and intravitreal chemotherapy for the left eye and focal adjuvant therapy (laser thermotherapy and cryotherapy) for both eyes. Six months after the last treatment, fundus examination showed a regressed tumor in both eyes. Ten months after the last treatment, except for in addition to tumor recurrence, rising intraocular pressure was noticed in the left eye. While doing IAC for the left eye, a very rapid growing yellowish dome-shaped mass was found which had doubled in size in two weeks. Enucleation was considered for her. RESULTS: Pathology evaluation of the enucleated eye revealed a very massive dome-shaped choroidal metastasis invasion with poorly differentiated RB tumor. Prophylactic systemic chemotherapy was performed for the patient. CONCLUSION: Choroidal metastasis in RB patients is often diagnosed based on pathology reports, but it may rarely be seen in clinical examinations especially if the pattern of tumor recurrence and growth is abnormal.

Correlation of Immunological Markers with Disease and Clinical Outcome Measures in Patients with Autoimmune Retinopathy.

Purpose: To determine if immunological markers (1) are significantly different between autoimmune retinopathy (AIR) patients and controls and (2) correlate with disease progression in AIR patients. Methods: We enrolled patients with a possible AIR diagnosis, as well as control participants without eye disease, autoimmunity, or cancer. Immunological markers were tested in all participants. In addition, AIR patients had up to three blood draws for testing over their disease course. For AIR patients, clinical measures, including visual acuity (VA) and Goldmann visual field (GVF) area, were recorded at each draw. We used the Mann-Whitney U test to compare the immunological markers between AIR patients and controls. We used multilevel mixed-effect regression to investigate the correlation between markers and clinical parameters over time in AIR patients. Results: Seventeen patients with AIR and 14 controls were included. AIR patients had a higher percent of monocytes (Z = 3.076, P = 0.002). An increase in immunoglobulin G against recoverin was correlated with a VA decrease (ß = 0.0044, P < 0.0001). An increase in monocyte proportion was correlated with a decrease in GVF area (ß = -7.27, P = 0.0021). Several markers of B-cell depletion were correlated with GVF improvement. Conclusions: Monocytes may play a role in AIR pathophysiology and be a disease activity marker. B-cell depletion markers correlated with clinical parameter improvement, particularly GVF. Translational Relevance: This work elucidates immunologic markers that may improve the accuracy of diagnosis and treatment of AIR.

Intravitreal Melphalan for Retinoblastoma: The Impact of Toxicity on Recurrence and Ultimate Globe Salvage.

INTRODUCTION: Intravitreal melphalan (IVM) has emerged as an efficacious treatment for vitreous seeding in retinoblastoma. Although rarely severe, IVM-related toxicity may be treatment limiting. There is paucity of data on the impact of IVM toxicity on new tumor formation and ultimate globe salvage. OBJECTIVES: To investigate whether the grade of retinal toxicity post-IVM impacts retinal and seeding tumor recurrence, as well as the overall ability to salvage the eye. METHODS: A single-institution retrospective chart review was performed on 47 eyes of 42 patients who received systemic intravenous chemotherapy followed by IVM as salvage treatment for persistent or recurrent vitreous seeding. Chorioretinal toxicity was graded from 0 to 5. RESULTS: Toxicity grade was inversely associated with the risk of recurrence, where a one-unit increase in toxicity grade correlated with nearly a 54% reduction in the odds of tumor recurrence (OR 0.46 [0.25-0.84], p = 0.01). Similarly, toxicity grade was related to enucleation, where a one-unit increase in toxicity grade was associated with a 31% reduction in the odds of undergoing enucleation (OR 0.69 [0.40-1.18], p = 0.17). CONCLUSIONS: While retinoblastoma therapy aims to limit toxicity, especially visually significant toxicity, eyes with higher grades of post-IVM toxicity are less likely to have retinal and seeding tumor recurrence.

Clinical Features and Multi-Modality Imaging of Isolated Retinal Astrocytic Hamartoma.

BACKGROUND AND OBJECTIVE: To identify the clinical and imaging characteristics of isolated retinal astrocytic hamartomas (IRAH). PATIENTS AND METHODS: A case series of eight patients diagnosed with IRAH. RESULTS: The average age at diagnosis was 32 years (range: 9 years to 80 years). After a median follow-up time of 59 months, none of the lesions had demonstrated any change or growth. Fundus fluorescein angiogram identified hyperfluorescence in five of six imaged lesions. Fundus autofluorescence (FAF) changes were seen in all eight cases. Ocular ultrasound was able to identify a lesion in only five of the seven cases. Optical coherence tomography (OCT) was able to document the tumor thickness and level of retinal invasion in all cases. CONCLUSIONS: Multimodal imaging is useful for the diagnosis and monitoring of IRAH. OCT and FAF are sensitivity tools for identifying IRA and can be used to follow the thickness and margins of these lesions. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e1-e9.].

Baseline choroidal thickness as a short-term predictor of visual acuity improvement following antivascular endothelial growth factor therapy in branch retinal vein occlusion.

PURPOSE: To evaluate the association between subfoveal choroidal thickness (SFCT) and branch retinal vein occlusion (BRVO) eyes treated with antivascular endothelial growth factor (anti-VEGF) therapy. METHODS: Retrospective cohort study of treatment naïve BRVO eyes treated with 3 monthly anti-VEGF injections. All patients received enhanced depth imaging spectral-domain optical coherence tomography scans to determine SFCT and central macular thickness (CMT). Baseline predictors (particularly SFCT) for functional response (best-corrected visual acuity (BCVA) gain ≥2 lines) were assessed at 3 months using univariate and multivariate analyses. RESULTS: Forty eyes from 39 patients were included. Mean baseline SFCT was higher in functional responders (240.4±73.1 µm), compared with both non-responders (193.3±63.6 µm; p=0.036) and their corresponding fellow eye (202.2±67.1 µm; p=0.022). A higher baseline SFCT (for every 100 µm increase in SFCT) was found to be a positive predictor for functional response (regression coefficient: 1.1; p=0.03) on univariate analysis but not multivariate analysis. A worse baseline BCVA (for every 0.1 logMAR increase) was a positive predictor for visual improvement with an adjusted OR of 1.30 (95% CI 1.03 to 1.63; p=0.0009) on multivariate analysis. CONCLUSIONS: Patients with BRVO with a worse initial BCVA are most likely to achieve visual improvement following anti-VEGF therapy. Additionally, baseline SFCT may also help predict which patients with BRVO have favourable visual outcomes. Patients with an initial choroidal thickness thicker than their fellow eye are more likely to have short-term visual improvement following treatment.

Cytogenetic results of choroidal nevus growth into melanoma in 55 consecutive cases.

PURPOSE: To investigate the cytogenetic results of choroidal nevus with photographically-documented transformation into choroidal melanoma. METHODS: Retrospective analysis of 55 consecutive patients who underwent fine needle aspiration biopsy (FNAB) for DNA isolation and whole genome array based assay for chromosomes 3, 6, and 8 analysis prior to plaque radiotherapy. Tumors with abnormalities in chromosomes 3 and 8 were considered high-risk for metastasis. RESULTS: At diagnosis of choroidal nevus the mean patient age was 57 years (median 57, range 10-83 years). All patients were Caucasian and 36 (65%) were female. At the time of nevus diagnosis, the mean tumor basal diameter was 7.4 mm (median 6.5, range 1.5-18.0 mm) and tumor thickness was 2.2 mm (median 2.2, range 0.5-3.9 mm). The mean interval between diagnosis of choroidal nevus and transformation into choroidal melanoma was 58 months (median 42, range 3-238 months). At the time of melanoma diagnosis, the mean tumor basal diameter was 9.7 mm (median 9.0, range 5.0-19.0) and tumor thickness was 3.5 mm (median 3.4, range 1.3-8.1). Cytogenetic analysis of FNAB-isolated melanoma revealed 25 patients (45%) with high-risk and 30 (55%) with low-risk cytogenetic findings. The rate of tumor growth into melanoma was inversely related to high-risk cytogenetic profile (p = 0.03) as those with fast transformation ≤ 1 year showed high-risk in 80% compared to those with slow transformation > 1 year whoshowed high-risk profile in only 38%. Fast transformation into melanoma conferred a relative risk (RR) of 2.116 for high-risk cytogenetic profile, compared to slow transformation. CONCLUSIONS: Choroidal nevus with rapid transformation into melanoma within 1 year is significantly more likely to demonstrate high-risk cytogenetic profile, at risk for metastatic disease, compared to those with slow transformation.

RHEGMATOGENOUS RETINAL DETACHMENT AFTER INTRAARTERIAL CHEMOTHERAPY FOR RETINOBLASTOMA: The 2016 Founders Award Lecture.

PURPOSE: To evaluate rhegmatogenous retinal detachment (RRD) in eyes with retinoblastoma after intraarterial chemotherapy (IAC). DESIGN: Retrospective case series. METHODS: Chart review. MAIN OUTCOME MEASURE: Development of RRD in the IAC era. RESULTS: Of 167 eyes in 157 consecutive patients, mean patient age at diagnosis of retinoblastoma was 19 months. Intraarterial chemotherapy was primary (75/167, 45%) or secondary (92/167, 55%). There were 10 eyes (10/167, 6%) that developed RRD after IAC. The RRD was mostly related to rapid tumor regression with atrophic retinal hole, occurring within one month (n = 8) or 12 months (n = 2) of IAC. Rhegmatogenous retinal detachment was found after primary (6/75, 8%) or secondary (4/92, 4%) IAC. Of primary cases, RRD was found in Group D (1/38 [3%], P = 0.1075) or Group E (5/30 [17%], P = 0.0348). For primary IAC (n = 75 eyes), RRD was found in endophytic (5/22 [23%], P = 0.0073), exophytic (0/29 [0%], P = 0.0760), or combined endophytic/exophytic pattern (1/24 [4%], P = 0.6575). A comparison of eyes with RRD (n = 10) versus without RRD (n = 157) found significant differences including greater mean age at presentation (38 vs. 18 months, P = 0.0522), greater 4-quadrant vitreous seeding (5/10, 50% vs. 27/157, 17%, P = 0.0236), and absence of subretinal fluid (3/10, 30% vs. 102/157, 65%, P = 0.0236). The cause of RRD was tumor regression-related atrophic retinal hole(s) in 7 (7/10, 70%) (unifocal [1/10, 10%] or multifocal [6/10, 60%] holes), cryotherapy-induced single atrophic hole in 2 (2/10, 20%), and single flap-tear from posterior vitreous detachment in one (1/10, 10%). In 4 (4/10, 40%) eyes with RRD, proliferative vitreoretinopathy was noted. The RRD was not related to intravitreal injection in any case, as in primary IAC no case had previous injection and in secondary IAC the injections were performed many months previously. Primary RRD repair involved pars plana vitrectomy in three, scleral buckle without drainage in one, laser barricade in one, and observation in five eyes. After 24 months mean follow-up, the retina showed complete reattachment (3/10, 30%), partial reattachment (2/10, 20%), and persistent detachment in all observed eyes (5/10, 50%). Enucleation was necessary for tumor recurrence (4/10, 40%) or neovascular glaucoma (1/10, 10%). There were no tumor-related metastases or death. CONCLUSION: After IAC for retinoblastoma, RRD occurs in 6%, mostly in advanced eyes with extensive endophytic tumor and generally from atrophic retinal hole after rapid tumor regression.

Baseline Choroidal Thickness as a Predictor for Treatment Outcomes in Central Retinal Vein Occlusion.

PURPOSE: To evaluate the association between initial subfoveal choroidal thickness and response to anti-vascular endothelial growth factor (anti-VEGF) therapy in central retinal vein occlusion (CRVO) eyes. DESIGN: Retrospective cohort study. METHODS: Forty-three eyes from 42 patients with treatment-naïve CRVO were included. All patients included were treated with a standard algorithm of 3 monthly anti-VEGF injections. Serial enhanced depth imaging optical coherence tomography scans were used to measure subfoveal choroidal thickness and central macular thickness (CMT). Baseline predictors (particularly choroidal thickness) for functional response (best-corrected visual acuity gain ≥2 lines) were assessed at 3 months follow-up using univariate and multivariate analyses. RESULTS: Forty-three eyes from 42 patients were included. Initial choroidal thickness in CRVO eyes (246 ± 102 µm) was greater than in their fellow eye (197 ± 86 µm; P = .023). In addition, mean choroidal thickness at baseline for functional responders (272.2 ± 107.3 µm) was greater than that of nonresponders (209.6 ± 85.8 µm; P = .039). A higher baseline choroidal thickness (for every 100-µm increase in choroidal thickness) was found to be a positive predictor for functional response (regression coefficient: 0.7; P = .04) on univariate analysis, whereas age (<70 years old) was the only positive predictor for functional response with an odds ratio of 6.49 (95% confidence interval: 1.11-38.1; P = .03) on multivariate regression analysis. CONCLUSIONS: Baseline choroidal thickness and age may help predict which patients with CRVO have favorable visual outcomes following short-term anti-VEGF therapy.

A single-nucleotide polymorphism in the MicroRNA-146a gene is associated with diabetic nephropathy and sight-threatening diabetic retinopathy in Caucasian patients.

AIMS: This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus. METHODS: Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, HbA1c and hypertension. RESULTS: A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93; CI 1.23-3.03; P = 0.004), but no association found in the T2DM group (OR 1.05; CI 0.83-1.32; P = 0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25; CI 1.03-1.53; P = 0.025). No association with DME was found in the T1DM group (OR 0.87; CI 0.54-1.42); P = 0.583), or with PDR for either type of DM. CONCLUSIONS: Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.

Promoter polymorphism at the tumour necrosis factor/lymphotoxin-alpha locus is associated with type of diabetes but not with susceptibility to sight-threatening diabetic retinopathy.

AIM: To investigate, in a large cohort of 2494 individuals with diabetes mellitus, whether functional single nucleotide polymorphisms in the promoter region of tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA) genes are associated with type of diabetes or presence of diabetic retinopathy. METHODS: A total of 334 type 1 diabetes and 999 type 2 diabetes participants with sight-threatening diabetic retinopathy, and 260 type 1 diabetes and 901 type 2 diabetes participants with no diabetic retinopathy or minimal non-proliferative diabetic retinopathy, were genotyped for two single nucleotide polymorphisms (rs1800629 and rs361525). RESULTS: The A allele of rs1800629 was associated with type 1 diabetes (p < 0.001; odds ratio = 0.62). After adjustment for age, sex, diabetes duration, HbA1c, hypertension and nephropathy, no significant association was found between rs1800629 or rs361525 and sight-threatening diabetic retinopathy. CONCLUSION: An association between the A allele of rs1800629 and type of diabetes was found. No association was found between two promoter variants of TNF and LTA, and diabetic retinopathy in a large cohort of Caucasian patients with type 1 diabetes and type 2 diabetes.

Common Sequence Variation in the VEGFC Gene Is Associated with Diabetic Retinopathy and Diabetic Macular Edema.

PURPOSE: To investigate associations between single nucleotide polymorphisms (SNPs) in the VEGFC gene and the development of diabetic retinopathy (DR) in white patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). DESIGN: Cross-sectional, case control study. PARTICIPANTS: White patients with T1DM or T2DM (n = 2899) were recruited from ophthalmology and endocrine clinics in Australia and the United Kingdom. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be receiving oral hypoglycemic treatment or insulin. METHODS: Participants were categorized according to their worst-ever DR grading, as having "no DR" (no history of nonproliferative DR [NPDR], proliferative DR [PDR], or diabetic macular edema [DME]) or "any DR" (further subclassified as NPDR or PDR, without or with DME). Clinical characteristics, glycemic control (hemoglobin A1c [HbA1c]), and presence of diabetic complications were determined at recruitment. Genotyping was performed for 13 VEGFC tag SNPs. MAIN OUTCOME MEASURES: Odds ratios (ORs) were determined for associations with DR of VEGFC tag SNPs, individually and within haplotypes. Logistic regression was used to adjust for clinical covariates, including DM type, age, sex, DM duration, hypertension, nephropathy, HbA1c, and smoking. RESULTS: Participants with DM but "no DR" (n = 980) were compared with 1919 participants with DM and "any DR." Three VEGFC SNPs were associated with DR after logistic regression: rs17697419 (P = 0.001; OR, 0.67; confidence interval [CI], 0.52-0.85), rs17697515 (P = 0.001; OR, 0.62; CI, 0.47-0.81), and rs2333526 (P = 0.005; OR, 0.69; CI, 0.54-0.90). rs17697515 Was also specifically associated with DME in those with T2DM (P = 0.004; OR, 0.53; CI, 0.35-0.82). Haplotype analysis revealed 2 significantly associated haplotypes, both protective against DR development. CONCLUSIONS: Significant associations were found between VEGFC tag SNPs (individually and within haplotypes) and the presence of any DR or DME in white participants with T1DM and T2DM.

Interobserver agreement in detecting spectral-domain optical coherence tomography features of diabetic macular edema.

PURPOSE: To evaluate interobserver agreement for the detection of spectral-domain optical coherence tomography (SDOCT) features of diabetic macular edema (DME). METHOD: Cross-sectional study in which 2 retinal specialists evaluated SDOCT scans from eyes receiving treatment for DME. Scans from 50 eyes with DME of 39 patients were graded for features of DME including intra-retinal fluid (IRF), diffuse retinal oedema (DRE), hyper-reflective foci (HRF), subretinal fluid (SRF), macular fluid and vitreomacular traction (VMT). Features were graded as present or absent at zones involving the fovea, 1mm from the fovea and the whole scan of 49 line scans. Analysis was performed using cross-tabulations for percentage concordance and kappa values (κ). RESULTS: In the 2950 line scans analysed, there was an increase in percentage concordance for DRE and HRF when moving from a foveal line scan, 1mm zone and then to a whole scan analysis (88% vs 94% vs 96%) and (88% vs 94% vs 94%) respectively with κ ranging from substantial to almost perfect. Percentage concordance for SRF was 96% at all 3 regions analysed, whilst IRF was 96% at fovea and 98% at higher number of line-scans analysed. Concordance for MF was 100% at fovea and 98% at 1mm zone and whole scan with almost perfect and substantial κ respectively. κ agreement was substantial for VMT at all regions analysed. CONCLUSION: We report a high level of interobserver agreement in the detection of SDOCT features of DME. This finding is important as detection of macular fluid is used to guide retreatment with anti-angiogenic agents.

Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) associated with B-cell lymphoma: report of a rare case.

BACKGROUND: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a paraneoplastic ocular syndrome occurring in patients with systemic, often occult but advanced carcinoma and is the hallmark of poor prognosis. Ocular signs precede manifestation of systemic carcinoma by 3-12 months, highlighting the need for appropriate index of suspicion and prompt evaluation. Treatment options for BDUMP are limited. Investigations are aimed at finding the occult primary malignancy, which can be challenging. Modalities for treatment of the ocular findings include corticosteroids, surgery, external beam radiotherapy, and treatment of the underlying malignant neoplasm. However, it is uncertain whether earlier intervention for the systemic malignancy will impact survival, as this paraneoplastic phenomenon is thought to occur in advanced malignancy. CASE PRESENTATION: We report a unique rare atypical case with BDUMP causing visual loss in a 62-year-old female as the presenting sign of central nervous system (CNS) B-cell lymphoma. Multiple grey or grey brown subretinal lesions with pigment clumps were present in both eyes on fundoscopy and multimodal imaging demonstrated multiple discrete lesions at the level of retinal pigment epithelium. Neuroimaging revealed presence of brainstem and cerebellopontine lesions suggestive of CNS lymphoma, which was further confirmed on biopsy. CONCLUSION: In the current atypical case, prompt diagnosis and immediate referral was key, with detailed systemic evaluation by an internist and oncologist. The reported case is distinct for the reason that BDUMP occurred secondary to primary CNS lymphoma, a hitherto unreported association.

Correlation of fundus fluorescein angiography and spectral-domain optical coherence tomography in identification of membrane subtypes in neovascular age-related macular degeneration.

AIMS: To assess the sensitivity and specificity of spectral-domain optical coherence tomography (SDOCT) for the determination of choroidal neovascularization (CNV) subtypes in neovascular age-related macular degeneration (AMD) compared to fundus fluorescein angiography (FFA) and also the agreement between the two procedures. DESIGN: This was a retrospective, observational study. METHODS: We evaluated and compared the CNV subtypes on FFA and OCT in 100 eyes initiated on ranibizumab for neovascular AMD. RESULTS: SDOCT showed high sensitivity (85.7-98.3%) and specificity (84.2-100%) compared to FFA in the diagnosis of the CNV subtype. The area under the receiver-operating characteristic curve ranged from 0.9 to 0.93 (p value <0.0001) for the different CNV subtypes. Weighted kappa statistics showed a near-perfect agreement of 0.85 between the procedures. CONCLUSION: SDOCT is a reliable tool for the diagnosis of CNV subtypes in neovascular AMD obviating the need for an invasive procedure such as FFA.

Giant cell arteritis presenting as choroidal infarction.

Background. Giant cell arteritis (GCA) is a systemic granulomatous vasculitis that affects large- and medium-sized arteries of the head and neck. Ocular manifestations of GCA usually are anterior ischaemic optic neuropathy (AION) or retinal vessel occlusion. Case Report. We report an interesting case of a 70-year-old man who presented with sudden vision loss and choroidal infarction in his left eye. Thorough clinical and paraclinical evaluation revealed an underlying GCA, the treatment of which prevented further vision loss and systemic complications. Conclusion. This is an unusual presentation of choroidal infarction associated with CGA and emphasizes the need of thorough systemic evaluation in patients with choroidal infarction.

Ocular disease awareness and pattern of ocular manifestation in patients with biopsy-proven lung sarcoidosis.

PURPOSE: The aim of this research is to study the patterns of ocular involvement in patients with biopsy-proven lung sarcoidosis and estimate the level of patients' awareness of possible ocular complications of sarcoidosis. METHODS: Fifty patients with biopsy-proven lung sarcoidosis were referred from the Department of Respiratory Medicine, University Hospital of Larissa, Greece. RESULTS: The most prominent ocular symptom was foreign body sensation in 15/50 patients (30%); only 6/50 of our patients (12%) were completely asymptomatic with respect to ocular symptoms. Anterior segment findings were: episcleritis in 8/50 patients (16%), iris nodules in 9/50 patients (18%), and cataract in 19/50 patients (38%). Periphlebitis was observed in 8/50 patients (16%), periarteritis in 8/50 patients (16%), epiretinal membrane in 6/50 patients (12%), and branch retinal vein occlusion in 7/50 of our patients (14%). Ten out of 50 patients (20%) had never visited an ophthalmologist before, whereas eight out of 50 patients (16%) had undergone an ophthalmic exam more than 2 years ago. CONCLUSIONS: Eye involvement is common in patient with biopsy-proven lung sarcoidosis and may occur even without prominent ocular symptoms.