Distribution of TGFBI variants in patients with early onset glaucoma.

Purpose: To describe a novel association of TGFBI variants with congenital glaucoma in a family with GAPO (growth retardation, alopecia, pseudoanodontia, and progressive optic atrophy) syndrome, as well as among other unrelated cases of juvenile onset open-angle glaucoma (JOAG) and primary congenital glaucoma (PCG). Methods: This study of one family of GAPO with congenital glaucoma and three unrelated patients with JOAG analyzed a common link to glaucoma pathogenesis. Three girls with GAPO syndrome born to consanguineous parents in a multi-generation consanguineous family were identified. Two of the girls had congenital glaucoma in both eyes, while the elder sibling (a 10-year-old female) had features of GAPO syndrome without glaucoma. Results: A genetic evaluation using whole exome sequencing revealed a novel homozygous ANTXR1 mutation in all three affected siblings with GAPO. No other mutations were detected in the genes associated with glaucoma. A rare missense variant in the TGFBI gene was shared in the two siblings with congenital glaucoma and GAPO syndrome. We found three other unrelated patients with JOAG and one patient with primary congenital glaucoma with no known glaucoma causing gene mutations, but having four different missense variants in the TGFBI gene. One of these patients with JOAG had familial granular corneal dystrophy. Molecular dynamic simulations of TGFBI and 3-D structural models of three of its variants showed significant alterations that could influence TGFBI protein function. Conclusions: The possibility that variations in the TGFBI gene could have a possible role in the pathogenesis of congenital and juvenile onset open-angle glaucomas needs further evaluation.

Vitreous Amyloidosis: Ocular, Systemic, and Genetic Insights.

PURPOSE: To report the unique clinical and surgical characteristics encountered in eyes with vitreous amyloidosis. Systemic evaluation and visual outcome after vitrectomy are discussed. A novel mutation in the transthyretin gene (TTR) in Indian patients with familial amyloid polyneuropathy (FAP) is described. DESIGN: Retrospective, observational study. PARTICIPANTS: Ten eyes of 5 patients from 2 pedigrees with a diagnosis of vitreous amyloidosis. METHODS: Detailed history, pedigree charting, systemic and ocular examination of 10 eyes (5 patients from 2 pedigrees) were carried out. Tests were performed to rule out vitreitis, retinal vasculitis, vitreous hemorrhage, and systemic amyloidosis. Genetic analysis to identify the mutation was performed in 1 patient. Vitreous biopsy, followed by 25-gauge pars plana vitrectomy, was performed in the same sitting in all cases. Samples were sent for Congo red staining and polarized microscopy. Patients were followed up on days 1, 7, and 28 and then every 2 months. Visual acuity assessment, intraocular pressure measurement, and fundus examination were performed each time. MAIN OUTCOME MEASURES: Mutations in TTR and postoperative visual acuity. RESULTS: Mean age at presentation was 32 years, with a 3:2 male-to-female distribution. Family history was positive in all patients. Nine eyes had pseudopodia lentis, whereas all 10 had glass wool-like vitreous. Glaucoma developed in 1 patient (2 eyes). Waxy paper-like vitreous with firm vitreous adhesions beyond major arcades and along retinal vessels was noted during surgery in all eyes. Congo red staining and apple green birefringence demonstrated vitreous amyloidosis. The mean preoperative best-corrected visual acuity (BCVA) was 1.39±0.64 logarithm of the minimum angle of resolution (logMAR), whereas the postoperative BCVA improved to 0.17±0.07 logMAR (P = 0.004). Gene sequencing revealed a phenylalanine→isoleucine mutation in the 33rd position of exon 2 of TTR in 1 patient of 1 pedigree, confirming the diagnosis of FAP. Two patients subsequently were found to have sensorimotor autonomic neuropathy, whereas 2 others had subclinical autonomic dysfunction. CONCLUSIONS: The clinical clues, management strategy, surgical characteristics, vitrectomy outcomes, and significance of systemic evaluation in vitreous amyloidosis are highlighted. A novel single mutation (Phe33Ile) in a case of FAP with vitreous amyloidosis from India is reported.

Intraocular use of bevacizumab in India: An issue resolved?

Bevacizumab is a monoclonal antibody against vascular endothelial growth factor (VEGF), which has been approved for intravenous use in certain cancers. There is evidence of its efficacy and safety as an intravitreal drug compared with ranibizumab and aflibercept. We have, in our practice, found it to be a cost-effective treatment option for ocular diseases, which could save a large amount of public money used in various national health insurance systems. An alert issued by the Drug Controller General of India led to a virtual ban on its intraocular use in India. However, pro-active advocacy and leadership by national ophthalmological societies helped to resolve the issue quickly.

Air bubble guide for adequacy of ophthalmic viscosurgical device during phacoemulsification.

Phacoemulsification in hard cataracts is a challenge. The use of dispersive ophthalmic viscosurgical devices (OVDs) to protect the endothelium is a routine step in such scenarios. However, as OVD is transparent, it is difficult to spot within the anterior chamber. Therefore, surgeons may not be aware when the OVD coating of the endothelium disappears during surgery. Consequently, there may be too frequent OVD injections, resulting in a waste of resources. On the contrary, the surgeon may fail to inject OVD at an appropriate time, leading to greater endothelial damage. We propose a novel technique of using an air bubble as a guide that helps in identifying the time when OVD disappears from the anterior chamber, thereby suggesting the surgeon to reinject before proceeding further.

Risk Factors for Descemet Membrane Endothelial Keratoplasty Rejection: Current Perspectives- Systematic Review.

Descemet membrane endothelial keratoplasty (DMEK) is a corneal endothelial transplantation procedure with selective removal of a patient's defective Descemet membrane and endothelium. It is replaced with a healthy donor Descemet membrane and endothelium without a stromal component. Corneal graft rejection can be at the level of epithelium, stroma as well endothelium. DMEK graft rejection is relatively less common than rejection with DSAEK or penetrating keratoplasty, and a good outcome may be achieved with prompt management. The clinical picture of DMEK rejection is usually similar to endothelial rejection in Descemet Stripping Endothelial Keratoplasty (DSEK/DSAEK), which generally manifests as pain, redness, reduction in visual acuity, stromal edema, endothelial rejection line, keratic precipitates at the back of the cornea and corneal neovascularization. However, more subtle forms of rejection or immune reactions are more common in DMEK compared to DSAEK eyes. Early clinical diagnosis, prompt intervention, and meticulous management safeguard visual acuity and graft survival in these cases. Intensive topical steroids form the mainstay in the management of DMEK rejection. Sometimes, oral or intravenous steroids or other systemic immunomodulators may be required. DMEK graft failure can be primary or secondary, and failure usually requires a second procedure in the form of repeat DMEK or DSEK or penetrating keratoplasty (PKP). A detailed literature search was performed using search engines such as Google Scholar, PubMed, and Google books, and a comprehensive review on DMEK rejection was found to be lacking. This review is a comprehensive update on the risk factors, pathophysiology, primary and secondary graft failure, recent advances in diagnosis, prevention of rejection, and updates in the management of DMEK rejection. The review also discusses the differential diagnosis of DMEK failure and rejection, prognosis, and future perspectives considering DMEK failure and rejection.

Analysis of choroidal thickness on optical coherence tomography in a patient with sudden-onset bilateral myopia, macular striae, and shallow anterior chamber after topiramate use.

This patient presented with sudden onset myopia, shallow anterior chamber, and radial macular folds in both eyes after using topiramate. Ocular parameters including increased choroidal thickness normalized after cessation of topiramate.

Knowledge, attitude, and practice patterns of Indian ophthalmologists regarding medicolegal issues.

PURPOSE: To assess the knowledge, attitude, and practice patterns (KAPP) of Indian ophthalmologists regarding medicolegal issues using an initial survey. METHODS: An online form was circulated among Indian ophthalmologists of all ages over social media and email by the Young Ophthalmologists Society of India (YOSI) and its medicolegal working group. Anonymous responses were obtained and analyzed for each question. The questionnaire comprised questions about demographic details, KAPP of medicolegal issues including how to deal with medicolegal issues (if faced), medical indemnity insurance, deviation from the recommended minimum sum assured (Rs. 1 crore for Indian ophthalmologists), and legal service providers. RESULTS: A total of 109 responses were obtained. The majority of the respondents were male (60, 55%). More than 50% of respondents (58, 53.2%) were younger than 35 years. More than one-fourth of the respondents were private practitioners (29, 27%), and the majority were of senior consultant designation (45, 41%). Around 80% of respondents (89, 81.6%) were aware of professional indemnity insurance; however, only 54% (n = 59) bought the insurance cover. A majority of the respondents (38, 64.4%) had an indemnity cover of a maximum of Rs. 50 lacs. Only 20% of respondents were aware of the expert body at the state/national level that deals with medicolegal cases. Thirty percent of respondents recommended the ideal cover amount to be more than Rs. 1 crore. CONCLUSION: The current survey highlights the dismally low rate of awareness of medicolegal issues among ophthalmologists. Specifically, a majority of Indian ophthalmologists surveyed did not have recommended minimum insured cover for professional indemnity insurance. Larger studies are needed to further explore KAPP of Indian ophthalmologists in various medicolegal issues.

Idiopathic Macular Hole: Algorithm for Nonsurgical Closure Based on Literature Review.

Our purpose is to review the closure time and optical coherence tomography (OCT) biomarkers that result in the non-surgical repair of idiopathic full-thickness macular holes (IFTMH). Our methodology consisted of a comprehensive literature review of the nonsurgical resolution of IFTMH followed by the calculation of the estimated closure time using the structural equation model. Forty-nine studies were found eligible yielding 181 eyes with IFTMH: 81.1% being small holes (<250 µm) with a median diameter of 166 µm. Final vision (mean 20/41) was related to initial vision (mean 20/65) and mean age (67 years). The hole diameter was correlated with initial vision and closure time (mean 3.9 months). Closure time was related to hole diameter and initial vision in the following algorithm: Closure time (month)= -0.057 + 0.008 diameter (µm) + 0.021 age (year) + 2.153 initial vision (logMAR). Biomarkers by OCT for self-closure included in decreasing frequency: pointed edge, de-turgescence of cystic macular edema (CME) with reversal of bascule bridge, and vitreomacular traction (VMT) release. The crucial function of Muller cell bridging in sealing the hole attests to its exceptional capacity for regeneration. After the hole has begun to close; however in less than 5%, a delayed restoration of the ellipsoid layer or a persistent outer foveal defect may prevent visual recovery and reopening of the hole is possible. In conclusion, eyes with small-size IFTMH and good baseline vision can have the additional option of close OCT monitoring for biomarkers of self-sealing biomarkers. When rehabilitative activity seems to be lacking, surgery is therefore mandatory.

Recovery course of persistent posterior subretinal fluid after successful repair of rhegmatogenous retinal detachment.

PURPOSE: To investigate best corrected visual acuity (BCVA), subretinal fluid (SRF) absorption time or ellipsoid zone (EZ) restoration time and various variables in patients with persistent SRF after successful primary repair of rhegmatogenous retinal detachment (RRD). METHODS: This retrospective multicenter study allowed independent analysis of the healing pattern by two observers based on composite of serial cross-sectional macular optical coherence tomography (OCT) scans. Univariate and multivariate analyses were implemented. RESULTS: One hundred and three cases had persistent SRF after pars plana vitrectomy, scleral buckling, or pneumatic retinopexy. By univariate analysis, SRF resolution time correlated positively with the number of retinal breaks (p < 0.001) and with increased myopia (p = 0.011). Using multivariate analysis, final BCVA (log MAR) correlated positively with age, duration of RRD, initial BCVA (OR = 3.28; [95%CI = 1.44-7.47]; p = 0.015), and SRF resolution time (OR = 0.46 [95%CI 0.21-1.05]; p = 0.049). EZ restoration time was longer with increasing number of retinal tears (OR = 0.67; [95%CI 0.29-1.52]; p = 0.030), worse final BCVA, and presence of macula-off RRD (OR = 0.26; [95%CI 0.08-0.88]; p = 0.056). SRF resolution time correlated marginally with prone position. CONCLUSIONS: Residual posterior SRF is more common in eyes with multiple breaks or in myopic eyes. Final BCVA is better in younger subjects and in eyes with shorter duration of RRD. Persistent SRF is a self-limited disorder with a mean resolution of 11.2 months with good visual prognosis improving from a mean baseline logMAR of 1.08 to 0.25 at one year.