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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.

Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS.Multicenter, international, prospective cohort study: ProgStar Study.Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS).Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β = -1.33; P.001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β = .09; P = .461).In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.

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 (β = 0.0044, P < 0.0001). An increase in monocyte proportion was correlated with a decrease in GVF area (β = -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.

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.

Purpose To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. Design Multicenter, international, prospective cohort study. Methods Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Prog ression of Star gardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. Results Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P = .99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg2) (95% CI, −1.23 deg2, 3.65 deg2; P = .33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. Conclusions Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.

PurposeTo evaluate the association between subfoveal choroidal thickness (SFCT) and branch retinal vein occlusion (BRVO) eyes treated with antivascular endothelial growth factor (anti-VEGF) therapy.MethodsRetrospective 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.ResultsForty 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.ConclusionsPatients 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.

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. Keywords: Choroidal nevus, Melanoma, Cytogenetic profile

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.

Heterozygous mutation in the PACS1 (phosphofurin acidic cluster sorting proteins 1) gene is a known cause of developmental delay, multiple congenital anomalies, dysmorphism, and ocular abnormalities. We present the case of an affected 10-year-old girl, conceived by assisted reproductive technology, who has ocular coloboma and findings characteristic of PACS1 mutation.

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. 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. 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. Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.

Purpose: Pigmentary maculopathy can occur in the context of various inherited and acquired diseases. Anterior segment dysgenesis arises due to developmental anomalies and may be associated with systemic disease, as in Rieger syndrome. Case report: A 49-year-old woman presented with longstanding reduction in vision, evidence of anterior segment dysgenesis, and multiple discrete pigmented lesions throughout the macula bilaterally. Electroretinographic findings were consistent with severe macular dysfunction. Gene array analysis did not reveal any chromosomal imbalances or other specific abnormalities. Conclusions: This is a unique case of bilateral pigmentary maculopathy and anterior segment dysgenesis, with clinical findings that are not characteristic of previously reported disease.

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.]

Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study.Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot.The top ranked variant was rs3805931 with p = 2.66 × 10(-7), but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10(-5)) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10(-8)). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina.Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.

Introduction The aim of this study was to investigate the frequency and duration of missed hospital appointments (MHAs) in a consecutive cohort of patients treated with ranibizumab for neovascular age-related macular degeneration (nAMD) and to assess their impact on outcomes of therapy in a real-world clinical setting. Methods Retrospective, cross-sectional study of consecutive patients attending medical retina clinics for nAMD treatment with ranibizumab. Results Seventy-eight eyes of 78 patients met the inclusion criteria for data analysis. Mean age was 78 years with mean follow-up of 27 months. Mean visual acuity (VA) was 52 ± 16 letters at baseline, 56 ± 17 letters at year 1 and 58 ± 16 letters at year 2. At the end of the second year, 90% of the patients had lost

This report reviews the genetics of familial exudative vitreoretinopathy (FEVR) and describes the identification of a novel variant in the LRP5 gene. A 20-month-old boy presented with reduced visual acuity in the right eye from exudative retinal detachment with mild retinal traction. Fluorescein angiography in the right eye disclosed extensive peripheral retinal non-perfusion and telangiectatic vessels and the left eye showed minimal peripheral non-perfusion. These features were suggestive of FEVR. Treatment with laser photocoagulation and cryotherapy to the region of non-perfusion was performed with resolution of the exudative retinal detachment. Fundus examination of the father revealed mild signs of FEVR, such as hyperacute retinal vascular branching and slight retinal vascular traction, whereas the mother's fundus examination was unremarkable. Genetic testing revealed that the affected boy was negative for mutations in the FZD4 , NDP , and TSPAN12 genes and heterozygous for a previously unreported A745V variant in the LRP5 gene. The father was also heterozygous for the A745V variant in the LRP5 gene and the unaffected mother showed no mutation. A genetic evaluation of the known genes associated with FEVR revealed a novel variant in the LRP5 gene that co-segregated with the phenotype in the family. [ J Pediatr Ophthalmol Strabismus . 2016;53:e39–e42.]

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.Retrospective cohort study.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.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.Baseline choroidal thickness and age may help predict which patients with CRVO have favorable visual outcomes following short-term anti-VEGF therapy.

To examine the association between characteristics of Stargardt disease and visual acuity (VA), to estimate the longitudinal rate of VA loss, and to identify risk factors for VA loss.Retrospective, multicenter cohort study.A total of 176 patients (332 eyes) with molecularly and clinically confirmed Stargardt disease enrolled from the United States and Europe.Standardized data report forms were used to collect retrospective data on participants' characteristics and best-corrected or presenting VA from medical charts. Linear models with generalized estimating equations were used to estimate the cross-sectional associations, and linear mixed effects models were used to estimate the longitudinal VA loss.Yearly change in VA.The median duration of observation was 3.6 years. At baseline, older age of symptom onset was associated with better VA, and a longer duration of symptoms was associated with worse VA. Longitudinal analysis estimated an average of 0.3 lines loss (P0.0001) per year overall, but the rate varied according to baseline VA: (1) eyes with baseline VA ≥20/25 (N = 53) declined at a rate of approximately 1.0 line per year; (2) eyes with VA between 20/25 and 20/70 (N = 65) declined at a rate of approximately 0.9 lines per year; (3) eyes with VA between 20/70 and 20/200 (N = 163) declined at a rate of 0.2 lines per year; and (4) eyes with VA worse than 20/200 (n = 49) improved at a rate of 0.5 lines per year. Older age of onset was associated with slower VA loss: Patients with onset age30 years showed 0.4 lines slower change of VA per year (P = 0.01) compared with patients with onset age ≤14 years.Given the overall slow rate of VA loss, VA is unlikely to be a sensitive outcome measure for treatment trials of Stargardt disease. However, given the faster decline in younger patients and those with no or mild visual impairment, VA may be a potential outcome measure for trials targeting such subgroups of patients. These observations will need to be assessed in a prospective study bearing in mind the inherent limitations of retrospective datasets.

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 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.

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.

Aim: To report a case of optic neuropathy secondary to Linezolid, second line anti tuberculosis agent. Case Report: 22 year Indian male with multidrug resistant spinal tuberculosis and TB meningitis was started on second line anti tuberculosis drugs. Within one month of onset of second line anti TB drug, he was noted to have optic neuropathy in both eyes. Visual field and electro diagnostics suggested optic neuropathy. Discussion: Linezolid is a synthetic oxazolidinone broad spectrum antibiotic and has been in off label use for multidrug resistant tuberculosis (MDR-TB). There are very scattered case reports of optic neuropathy secondary to use of this off label drug. In our case, the optic neuropathy was however reversible on stoppage of the drug. Conclusion: It seems prudent that baseline ophthalmological evaluation to be done for all patients to be subjected for treatment with this drug for any short term or long term therapy.

Objective To explore the impact of weekly transcorneal electrical stimulation (TES) over a 6-month period as a treatment for retinitis pigmentosa (RP). Methods and analysis A prospective open-label observational trial was carried out assessing weekly TES in participants with RP for a period of 6 months followed by observation for a further 6 months. Clinical examination and investigations were carried out at 3 monthly intervals for a total of 12 months. The primary outcome measure explored safety through a descriptive analysis of adverse effects with secondary outcome measures evaluating structural and functional efficacy. Results Seven male and seven female participants with RP aged 18–80 years were recruited. TES was well tolerated with no serious adverse events reported. Two participants reported transient foreign body sensation and one participant had discomfort underneath the skin electrode. Following 6 months of TES, best-corrected visual acuity increased by 1.1±1.4 letters in the control arm and 0.93±1.4 letters in the treated arm. Central microperimetry threshold sensitivity rose by 0.02±0.5 decibels (dB) and 0.37±0.4 dB and Goldmann visual field volume by 0.16±0.09 steradians (sr) vs 0.22±0.12 sr for the control and treated eye, respectively. There was no statistical significance seen between eyes following the treatment or observation period. Conclusion This small open-label clinical trial showed that TES was safe and well tolerated in patients with RP. Visual function measurements at 6 months demonstrated no significant difference between the control and treated eyes. The results justify a larger clinical trial over a longer period of time in order to identify any treatment effect.

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.

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.

Introduction. Bilateral intracavernous carotid artery aneurysms (ICAAs) are extremely rare and difficult to treat.Case Report. A 26-year-old female presented in our clinic with acute diplopia due to oculomotor nerve palsy on the left side. Magnetic resonance imaging of the brain showed two heterogeneously enhanced masses indicating bilateral ICAA. An endovascular coil embolization was performed on the left side successfully, resulting in resolution of her symptoms.Conclusion. Thorough systemic evaluation in young patients with diplopia can reveal life-threatening underlying pathology and prevent major complications.

Fani Zacharaki,1 Georgios M Hadjigeorgiou,2 Georgios G Koliakos,3 Margaux A Morrison,4 Aspasia Tsezou,5 Dimitrios Z Chatzoulis,1 Pavlina Almpanidou,1 Konstantina Topouridou,3 Constantinos H Karabatsas,1 Maria Pefkianaki,1 Margaret M DeAngelis,4 Evangelia E Tsironi1 1Department of Ophthalmology, 2Department of Neurology, Faculty of Medicine, University of Thessaly, Larissa, 3Department of Biochemistry, Medical School, Aristotles University of Thessaloniki, Thessaloniki, Greece; 4Department of Ophthalmology and Visual Sciences, John A Moran Eye Center, University of Utah, Salt Lake City, UT, USA; 5Department of Biology, Faculty of Medicine, University of Thessaly, Larissa, Greece Background: The purpose of this study was to investigate plasma homocysteine levels and polymorphisms in genes encoding enzymes in the metabolic pathway of homocysteine in association with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXFG). Methods: A total of 156 glaucoma patients (76 with POAG and 80 with PXFG) and 135 controls matched for age and sex were enrolled in this study. Plasma homocysteine levels were measured using a commercially available enzyme-linked immunosorbent assay kit. DNA was extracted from peripheral blood leukocytes and real-time polymerase chain reaction was performed for genotyping of the samples. Patients were genotyped using predesigned TaqMan® single nucleo­tide polymorphism genotyping assays for two exon variations (rs1801131, rs1801133) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and one intron variation (rs8006686) in the methylenetetrahydrofolate dehydrogenase (MTHFD1) gene.Results: Homocysteine levels were slightly higher in the patient group (POAG and PXFG) compared with controls, but the difference did not reach statistical significance. The minor alleles of the MTHFR single nucleotide polymorphisms showed a protective effect for POAG and showed an increased risk for PXFG, but none of these associations reached statistical significance (P>0.05). The minor allele of MTHFD1 rs8006686 showed a trend for increased risk of both POAG and PXFG (P>0.05). No statistically significant interaction was seen between the genetic variants and homocysteine levels (P>0.05). Conclusion: Our results show that neither the examined single nucleotide polymorphisms from genes involved in the pathway of homocysteine metabolism nor the measured homocysteine levels were associated with POAG or PXFG in our study cohort. Keywords: homocysteine, glaucoma, polymorphisms

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 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.

Purpose To measure foveal avascular zone (FAZ) dimensions in healthy eyes using optical coherence tomography angiography (OCTA) and calculate interobserver variability. Design Reliability analysis. Methods Thirty-four eyes of 17 healthy subjects underwent OCTA at the Retina Service of Wills Eye Hospital. Two masked graders performed measurements of FAZ dimensions including area, perimeter, and maximum horizontal and vertical diameters using ImageJ. Intraclass correlation coefficient (ICC) between graders was calculated. Results Mean area (mm 2 ), perimeter (mm), and maximum horizontal and vertical diameters (mm) were 0.27 ± 0.101, 2.21 ± 0.451, 0.59 ± 0.126, and 0.56 ± 0.118, respectively, at the superficial and 0.34 ± 0.116, 2.50 ± 0.462, 0.69 ± 0.123, and 0.63 ± 0.110 at the deep network. Interobserver agreement was high for all superficial FAZ measurements (ICC ≥0.90) but did not meet the lowest acceptable grader agreement for the deep vascular network (ICC P > .05). Conclusion Manual measurement of FAZ dimensions using OCTA is a noninvasive and reliable method for quantifying FAZ at the superficial vascular network. Assessing FAZ alterations in the deep vascular network may be subject to greater interobserver variability.

Background To evaluate the reliability and construct validity of a Greek version of the NEI-VFQ-25 in patients with chronic ophthalmic diseases. Methods We developed the Greek version of the instrument using forward and backward translation. One hundred-eighty-six patients responded to the questionnaire. To examine reliability, Cronbach's alpha for each subscale was used as an index of internal consistency. Test-retest reliability was evaluated with intraclass correlation coefficients. Regarding construct validity, both convergent and discriminant validities were calculated by means of multi-trait analysis. Rasch analysis was used to estimate the visual ability required by each item for a particular response, and each patient's visual ability. Correspondingly, instrument validity was evaluated by estimating the distribution of residuals for item and subject measures. Results Four patient groups were studied, each including participants with a single cause of visual impairment. Group 1 consisted of 84 glaucoma subjects. Group 2 included 30 subjects with age-related macular degeneration (ARMD); group 3 included 25 subjects with dry-eye syndrome, whereas group 4 included 18 cataract patients. Twenty-nine healthy individuals comprised the control group. NEI-VFQ scores (mean ± SD) for the glaucoma, ARMD, dry-eye, cataract and control groups were: 76.9 ± 20.2, 70.9 ± 20.2, 81.6 ± 16.5, 73.5 ± 24.0 and 93.7 ± 8.9 respectively. Item analysis revealed no significant data skewing. Cronbach's alpha ranged from 0.678 to 0.926, with most subscales having high internal consistency. Intraclass correlation coefficient ranged from 0.717 to 0.910 for all subscales. All items passed the convergent and discriminant validity tests. Strong correlations were detected between visual acuity and "general vision", "distant activities" and "near activities" subscales. Significant correlations were also detected between visual field deficits and the "peripheral vision" and "general vision" subscales. Rasch analysis revealed potential weaknesses of the instrument that are associated with the assumptions of the model itself. Specifically, low precision of the "agreement" items was detected in the estimation of visual ability. Twenty-three percent of the subjects had fit statistics that fell outside the tolerance box. Conclusion Although traditional validation methods indicated that the Greek version of the NEI-VFQ-25 is a valid and reliable instrument for VS-QoL assessment, Rasch analysis detected significant misfits to the model, especially of the "agreement" items. This means that results of the corresponding subscales should be interpreted with extreme caution.

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.

Introduction Antiphospholipid syndrome is an autoimmune disorder characterized by either a history of vascular thrombosis (one or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ) or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The systemic features of the syndrome are characterized by large variability depending on the affected organ(s). Among them, neurological and behavioural disturbances, dermatological features as livedo reticularis and renal, ocular, liver or valvular heart manifestations have been reported in antiphospholipid syndrome patients. However, studies on the frequency and clinical presentation of the ocular manifestations as the prevailing (first) sign of antiphospholipid syndrome in patients suffering from "unexplained" ocular disease are missing. Herein, we present three cases suffering from unexplained ocular disease as first manifestation of antiphospholipid syndrome. Case presentation All the three patients were referred to our department because of unexplained ocular features from the anterior or posterior segment and unexplained neuro-ophthalmologic symptoms. The first patient had bilateral retinal occlusive disease, the second and the third patient had unilateral nonarteritic anterior ischemic optic neuropathy with macular oedema. Moderate to high levels of antiphospholipid antibodies were detected in all of them at baseline as well as 6 to 12 weeks after initial testing confirming the presence of antiphospholipid antibodies. Anticoagulant treatment with acenocoumarol was instituted resulting in stabilization and/or improvement of ocular signs in all of them. Conclusion Due to the important diagnostic and therapeutic implications of antiphospholipid syndrome, the possibility of ocular features as the first clinical manifestation of antiphospholipid syndrome should be kept in mind of the physicians particularly in patients with no evident risk factors for ocular disease. In this case, prompt anticoagulant treatment and close follow-up seem to be essential for vision salvation and stabilization.