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.

Genome-wide association study for sight-threatening diabetic retinopathy reveals association with genetic variation near the GRB2 gene.

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS/INTERPRETATION: 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.

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.

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.

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.

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.

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.

Evaluation of MMP1 and MMP3 gene polymorphisms in exfoliation syndrome and exfoliation glaucoma.

PURPOSE: To investigate possible genetic associations of matrix metalloproteinase-1 (MMP1) and MMP3 gene polymorphisms with exfoliation syndrome (XFS) with (XFS/+G) and without (XFS/-G) glaucoma in a cohort of Greek patients. METHODS: A total of 182 unrelated Greek patients with XFS, including 92 patients with XFS/+G, and 214 unrelated age- and gender-matched controls were enrolled in the study. MMP1 -1607 1G/2G (rs1799750) and MMP3 -1171 5A/6A (rs3025058) polymorphisms were determined using standard PCR/restriction fragment length polymorphism methods. Differences in allele and genotype distributions were analyzed using logistic regression. RESULTS: The distribution of genotypes and alleles in MMP1 and MMP3 polymorphisms was not significantly different between cases with exfoliation syndrome, with or without glaucoma, and controls. However, the allele contrast for the MMP1 variant showed a trend for a significant association with XFS/-G (Odds Ratio=1.47 [1.03-2.10]), since after correction for multiple comparisons, this association was no longer statistically significant. CONCLUSIONS: Our study provided some evidence of a possible role of the MMP1 variant in the development of exfoliation syndrome in Greek patients.

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.

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.].

Psychometric properties of the Greek version of the NEI-VFQ 25.

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.

An unusual case of bilateral pigmented maculopathy and anterior segment dysgenesis.

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.

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.

Ocular manifestations of PACS1 mutation.

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.

Transcorneal electrical stimulation for the treatment of retinitis pigmentosa: results from the TESOLAUK trial.

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.

Measurement of Foveal Avascular Zone Dimensions and its Reliability in Healthy Eyes Using Optical Coherence Tomography Angiography.

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 <0.85). Fellow eyes had statistically similar values (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.

Familial Exudative Vitreoretinopathy With a Novel LRP5 Mutation.

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.].