Typical best vitelliform dystrophy secondary to biallelic variants in BEST1.

BACKGROUND: Pathogenic variants in BEST1 can cause autosomal dominant or autosomal recessive dystrophy, typically associated with distinct retinal phenotypes. In heterozygous cases, the disorder is commonly characterized by yellow sub-macular lesions in the early stages, known as Best vitelliform macular dystrophy (BVMD). Biallelic variants usually cause a more severe phenotype including diffuse retinal pigment epithelial irregularity and widespread generalized progressive retinopathy, known as autosomal recessive bestrophinopathy (ARB). This study describes three cases with clinical changes consistent with BVMD, however, unusually associated with autosomal recessive inheritance. MATERIALS AND METHODS: Detailed ophthalmic workup included comprehensive ophthalmologic examination, multimodal retinal imaging, full-field and pattern electroretinography (ERG; PERG), and electrooculogram (EOG). Genetic analysis of probands and segregation testing and fundus examination of proband relatives was performed where possible. RESULTS: Three unrelated cases presented with a clinical phenotype typical for BVMD and were found to have biallelic disease-causing variants in BEST1. PERG P50 and ERG were normal in all cases. The EOG was subnormal (probands 1 and 3) or normal/borderline (proband 2). Probands 1 and 2 were homozygous for the BEST1 missense variant c.139C>T, p.Arg47Cys, while proband 3 was homozygous for a deletion, c.536_538delACA, p.Asn179del. The parents of proband 1 were phenotypically normal. Parents of proband 1 and 2 were heterozygous for the same missense variant. CONCLUSIONS: Individuals with biallelic variants in BEST1 can present with a phenotype indistinguishable from BVMD. The same clinical phenotype may not be evident in those harboring the same variants in the heterozygous state. This has implications for genetic counselling and prognosticationA.

Closure rate and recovery of subfoveal microstructures following conventional internal limiting membrane peeling versus per fluoro octane-assisted inverted flap for large macular holes - A randomized controlled trial (InFlap Study).

PURPOSE: To analyze the outcomes following conventional internal limiting membrane (ILM) peeling versus perfluoro octane-assisted inverted flap technique for large macular holes (MH). METHODS: A consecutive 99 eyes of 99 patients were enrolled {45 - conventional group and 54 - inverted flap (InFlap) group}. The primary outcome was a difference in closure rate. Secondary outcomes were differences in best-corrected visual acuity (BCVA), restoration of external limiting membrane (ELM) and ellipsoid zone (EZ) between groups at 3 (primary endpoint), 6 and 12 (secondary endpoints) months. Additionally, the effect of different gas tamponades on closure rates, ILM flap disintegration in InFlap group, and subfoveal thickness (SFT) between groups in closed. RESULTS: At 3 months, there was no difference in the closure rate and BCVA between groups. At six months, closure rate was significantly better in the InFlap group. However, this difference was not maintained at 12 months. There was no difference in BCVA between groups at any visit. The ELM recovery was significantly higher in the conventional group at three months; however, there was no difference in ELM/EZ recovery between groups at other visits. The closure rate in the InFlap group was the same irrespective of gas tamponade. The ILM flap was identifiable in one-third of patients at 12 months. In closed MH, SFT was significantly more in InFlap group. CONCLUSION: The closure rate and visual outcomes remained similar in both groups in the immediate and long term. Conventional ILM peeling technique seems to have early ELM recovery when compared to inverted flap technique.

Subjective and objective measures of the patient experience before, during, and after intravitreal anti-vascular endothelial growth factor injections.

Purpose: To assess patient experience of intravitreal injections using vital-signs, visual-experience, pain-rating and emotional response during intravitreal anti-VEGF injections. Methods: A prospective observational study of patient experience of intravitreal anti-VEGF injections done following metrics were collected pre-injection, during injection, and post-injection: pain assessment using visual analog score, fear-response rating, visual-experience questionnaire, and vital-signs. Results: A total of one-hundred-and-seventy-four patients undergoing intravitreal anti-VEGF injections for retinal pathologies were included in the study. Mean age was 58.8 ± 10.4 years in <5 injection group (n = 133) and 59.02 ± 9.0 years in ≥5 injection group (n = 41) (P = 0.90).During injection, 90.2% of patients in <5 injection group reported moderate or severe pain compared to 78% of patients in ≥5 injection group. In pre and post-injection phases, mild-to-moderate pain was reported in both groups (P = <0.001). Ninety-two (52.9%) patients reported having a mild frightening experience. There was no statistical significance in patients assessment of fear with respect to age, sex, or number of injections. The Systolic Blood Pressure (SBP) during and following injection ((SBP 171.7 ± 21.1,150.8 ± 16.2) procedures was significantly higher in cases with <5 injections when comparing to cases with >5 injections (SBP 159.7 ± 26.4, 143.2 ± 17.0) (P = 0.003), (P = 0.011). DBP, heart rate, pulse rate measurements were similar among patients in all phases of the study. Conclusion: We report a large sample size with comprehensive assessments of the patient experience. Higher pain ratings in the <5 injection group, the increase in the SBP in the pre-and during injection phases, and the overall rating of mild-to-moderate fear during the procedure.

Genetic characterization of Stargardt clinical phenotype in South Indian patients using sanger and targeted sequencing.

BACKGROUND: Stargardt disease 1 (STGD1; MIM 248200) is a monogenic form of autosomal recessive genetic disease caused by mutation in ABCA4. This gene has a major role in hydrolyzing N-retinylidene-phosphatidylethanolamine to all-trans-retinal and phosphatidylethanolamine. The purpose of this study is to identify the frequency of putative disease-causing mutations associated with Stargardt disease in a South Indian population. METHODS: A total of 28 clinically diagnosed Stargardt-like phenotype patients were recruited from south India. Ophthalmic examination of all patients was carefully carried out by a retina specialist based on the stages of fundus imaging and ERG grouping. Genetic analysis of ABCA4 was performed for all patients using Sanger sequencing and clinical exome sequencing. RESULTS: This study identified disease-causing mutations in ABCA4 in 75% (21/28) of patients, 7% (2/28) exhibited benign variants and 18% (5/28) were negative for the disease-causing mutation. CONCLUSION: This is the first study describing the genetic association of ABCA4 disease-causing mutation in South Indian Stargardt 1 patients (STGD1). Our findings highlighted the presence of two novel missense mutations and an (in/del, single base pair deletion & splice variant) in ABCA4. However, genetic heterogeneity in ABCA4 mutants requires a larger sample size to establish a true correlation with clinical phenotype.

Barriers in utilisation of low vision assistive products.

AIM: To understand the barriers in utilisation of low vision assistive products (LVAPs) from the perspective of patients with low vision. METHODS: Patients referred to low vision clinic in a tertiary eye care hospital in India who were prescribed LVAPs but were un-willing to accept the products were interviewed using questionnaires. Data pertaining to the age, diagnosis, gender, occupation, preferred LVAPs, patient's perception of vision loss and the primary reason for non-acceptance of LVAPs were analysed. RESULTS: A total of 235 among the 413 patients who noticed improvement in visual performance with LVAPs were unwilling to utilise these products. The questionnaire revealed that 53% of the patients who felt they were not candidates for LVAPs were experiencing severe visual impairment (p < 0.02). Non-acceptance was highest (68.6%) in patients < 15 years of age. The most common causes of non-acceptance were social stigma in patients < 40 years (41.3%; p < 0.0001), fear of loss of employment in patients 41-60 years (26.6%; p < 0.01) and low necessity in patients > 60 years (25%; p < 0.001). Denial of the magnitude of their illness was more common in patients above 60 years (16.5%). Non-acceptance rate was lowest for macular disorders (39.6%) and highest for retinitis pigmentosa (81%). Among devices, hand and stand magnifiers had the lowest non-acceptance rate (41%). Telescopes and electronic devices had the highest rate of non-acceptance (92% and 89%, respectively). CONCLUSION: Reasons for poor utilisation of LVAPs are multifactorial extending beyond affordability or accessibility. Knowledge of these barriers can help in creating content for awareness campaigns among patients, healthcare professionals and general society. Further research is necessary on the psychological and psycho social contributors to this process.

Encapsulated metallic intraocular foreign body of long duration presenting with cystoid macular edema and normal full-field electroretinogram.

The purpose of the study is to report an unusual case of encapsulated iron intraocular foreign body (IOFB) of long duration presenting with cystoid macular edema (CME) and normal full-field electroretinogram (ERG). A 28-year-old male presented with a history of metal injury 5 years back and subsequent visual loss in the left eye for 3 months. Fundus examination of the left eye showed an encapsulated cyst-like structure inferior to the disc with the surrounding pigmentary changes and CME. B-scan ultrasonography and computed tomography scan confirmed metallic IOFB. A full-field ERG performed before surgery showed a normal response. He underwent pars plana vitrectomy with IOFB extraction and silicone oil injection as a tamponade. Two months later, silicone oil removal was combined with intravitreal triamcinolone acetonide (IVTA) injection for persistent edema. Meticulous clinical evaluation, imaging, electrophysiological testing coupled with surgical intervention, and IVTA injection resulted in resolution of CME with minimal visual improvement. In conclusion long-standing encapsulated iron IOFB on the retina can cause vision-threatening complications without siderosis.

Diffuse unilateral subacute neuroretinitis.

Diffuse unilateral subacute neuroretinitis (DUSN) is a subacute outer retinal inflammation due to the presence of a subretinal worm. The worm is identifiable in only 30% of the cases. The identification of the worm and laser photocoagulation of the worm remains the mainstay of treatment. Here, we describe a case of DUSN with a subretinal worm in the macula which was captured on Optical coherence tomography (OCT) scans and treated with laser photoooagulation.

Combined Cataract Extraction With Pars Plana Vitrectomy and Metallic Intraocular Foreign Body Removal Through Sclerocorneal Tunnel Using a Novel "Magnet Handshake" Technique.

PURPOSE: To study the outcomes of combined cataract extraction with pars plana vitrectomy (PPV) and metallic intraocular foreign body (IOFB) removal through a sclerocorneal tunnel using the "magnetic handshake" technique. DESIGN: A retrospective review. METHODS: Retrospective review of case records of 14 patients from 2010 to 2016 with metallic IOFB and traumatic cataract was performed. Cataract extraction was combined with PPV. Two intraocular magnets (IOMs) introduced through 20-gauge vitrectomy port and sclerocorneal tunnel helped achieve safe delivery of IOFB outside the globe by the "magnetic handshake" technique. RESULTS: All patients were males with a mean age of 33.04 years. A final best corrected visual acuity (BCVA) of 20/60 or better was noted in 10 (71.42%) of 14 patients. Final reattachment with more than 1 surgery was achieved in 13 (92.85%) patients. Postoperative complications included retinal detachment (RD) and phthisis bulbi in 1 (14.28%) patient each. CONCLUSIONS: Combined cataract extraction with PPV and metallic IOFB removal through sclerocorneal tunnel using the "magnet handshake" technique gives good visual and surgical outcomes.

Genetic risk factors for late age-related macular degeneration in India.

BACKGROUND/AIMS: There are limited data from India on genetic variants influencing late age-related macular degeneration (AMD). We have previously reported associations from a population-based study in India (the India age-related eye disease study (INDEYE)) of early AMD and single nucleotide polymorphisms (SNPs) in ARMS2/HTRA1 and no association with CFH, C2 or CFB. Late AMD cases were too few for meaningful analyses. We aimed to investigate SNPs for late AMD through case enrichment and extend the loci for early AMD. METHODS: Fundus images of late AMD hospital cases were independently graded by the modified Wisconsin AMD grading scheme. In total 510 cases with late AMD (14 geographic atrophy and 496 neovascular AMD (nvAMD)), 1876 with early AMD and 1176 with no signs of AMD underwent genotyping for selected SNPs. We investigated genotype and per-allele additive associations (OR and 95% CIs) with nvAMD or early AMD. Bonferroni adjusted P values are presented. RESULTS: We found associations with nvAMD for CFHY402H variant (rs1061170) (OR=1.99, 95% CI 1.67 to 2.37, P=10-6), ARMS2 (rs10490924) (OR=2.94, 95% CI 2.45 to 3.52, P=10-9), C2 (rs547154) (OR=0.67, 95% CI 0.53 to 0.85, P=0.01), ABCA1 (rs1883025) (OR=0.77, 95% CI 0.65 to 0.92, P=0.04) and an SNP near VEGFA (rs4711751) (OR=0.64, 95% CI 0.54 to 0.77, P=10-3). We found no associations of TLR3 (rs3775291), CFD (rs3826945), FRK (rs1999930) or LIPC (rs10468017) or APOE ε4 alleles with nvAMD or early AMD, nor between early AMD and rs1883025 or rs4711751. CONCLUSIONS: The major genetic determinants of nvAMD risk in India are similar to those in other ancestries, while findings for early AMD suggest potential differences in the pathophysiology of AMD development.

Acute angle closure glaucoma secondary to polypoidal choroidal vasculopathy - a devastating complication.

Acute angle closure glaucoma (ACG) in the setting of polypoidal choroidal vasculopathy (PCV) is a catastrophic complication that has been documented infrequently in literature. Ours is the second only report that describes hemorrhagic choroidal detachment as an event leading to acute angle closure glaucoma in PCV patients and the first one to describe the use of diode cyclophotocoagulation (CPC) for this condition. The purpose of this article is to familiarize readers with this entity that has an extremely dismal visual prognosis. Ours is a descriptive case report of two patients with PCV complicated by sudden onset hemorrhagic choroidal detachment (CD) and acute ACG. Both patients had severe pain with no perception of light at presentation with an acute angle closure attack. Both underwent diode CPC for pain relief and control of intraocular pressure (IOP). Both our patients did not regain any vision, but their pain was relieved by diode CPC. Both eyes eventually became phthisical. Acute ACG following massive hemorrhagic CD is a rare but grave complication of PCV, not amenable to treatment. Diode CPC is an effective palliative modality of management to achieve pain relief in such cases.

Traumatic endophthalmitis following a crane pecking injury - An unusual mode.

PURPOSE: To report a case of beta-hemolytic streptococcal endophthalmitis following crane-pecking injury. CASE REPORT: A twelve-year-old boy was brought to us by his father with history of crane beak injury in his right eye. On examination, his vision was 6/24 Snellen's acuity. Anterior segment examination showed a full thickness two mm corneo-limbal tear at 1 o'clock with iris prolapse. Pupil showed peaking through the wound with a clear crystalline lens. There was no evidence of hypopyon in the anterior chamber and B-scan ultrasonography showed acoustically clear vitreous with an attached retina. Left eye was within normal limits. Primary corneo-limbal tear repair was performed within 24 hours from the time of presentation. Intra-operatively, the corneal surgeon noted turbid aqueous with minimal hypopyon. In view of clinical suspicion of infection, an intravitreal tap for culture was taken during the primary repair, and prophylactic intravitreal antibiotics were given. The culture report showed beta-hemolytic streptococci. Pars plana vitrectomy with intravitreal antibiotics was performed after 2 days as serial ultrasound scans showed appearance and worsening of endophthalmitis. A month after the surgery, his best corrected visual acuity improved to 6/12. CONCLUSION: Ocular injuries resulting from bird pecking are very rare. We treated a case of full thickness corneo-limbal tear with endophthalmitis caused by beta-hemolytic streptococci following a crane-pecking injury. We recommend that injecting intravitreal antibiotics along with primary globe repair in case of severe/contaminated injuries and early pars plana core-vitrectomy would result in better outcome like in our case.