Endoilluminator-aided cataract surgery in eyes with corneal opacity - A modified surgical approach.

Background: Cataract and corneal blindness continue to be leading causes of reversible blindness in India. These can co-exist in a multitude of pathologies such as trauma, healed keratitis (old herpetic scar), chronic degenerative changes such as labrador keratopathy, bullous keratopathy, corneal dystrophies etc. Phacoemulsification in such eyes is rewarding to the patient in terms of minimal intervention, less risk of complications owing to reduced open sky time (as in case of combined keratoplasty), and better predictable visual outcomes. Approach to such eyes with poor visualisation is highly challenging. Purpose: We illustrate a modified surgical technique of chandelier illumination through pars plana for cataract surgery in eyes with corneal opacity of varying grades. Synopsis: Five patients with dense cataract and small pupils, associated with corneal opacity (leucomatous and macular grade) are described. Closed chamber phacoemulsification with intraocular lens with or without pupil expanders was performed assisted by 23 or 25 gauge pars plana chandelier illumination introduced in the vitreous cavity through a sclerotomy wound made prior to phacoemulsification in the inferotemporal quadrant. Highlights: Chandelier illumination aids in reducing the light scatter that occurs due to corneal opacity. Ease of visualisation of lens structures and of performing cataract surgery was noticed. One case was combined with penetrating keratoplasty with reduced open sky time. This assisted technique has advantages such as enhancing visualisation intraoperatively and allowing working in closed chamber. Its self-retaining nature aids bimanual manipulation. No complications were encountered. The video highlights the utility, advantages and practicality of chandelier retroillumination in patients with corneal opacities of varying degree undergoing phacoemulsification. Video Link: https://youtu.be/I3z6QG-_wD8.

A deep dive into the latest European Glaucoma Society and Asia-Pacific Glaucoma Society guidelines and their relevance to India.

Glaucoma is the second leading cause of blindness in India. Despite advances in diagnosing and managing glaucoma, there is a lack of India-specific clinical guidelines on glaucoma. Ophthalmologists often refer to the European Glaucoma Society (EGS) and Asia-Pacific Glaucoma Society (APGS) guidelines. A group of glaucoma experts was convened to review the recently released EGS guideline (fifth edition) and the APGS guideline and explore their relevance to the Indian context. This review provides the salient features of EGS and APGS guidelines and their utility in Indian scenario. Glaucoma diagnosis should be based on visual acuity and refractive errors, slit-lamp examination, gonioscopy, tonometry, visual field (VF) testing, and clinical assessment of optic nerve head, retinal nerve fiber layer (RNFL), and macula. The intraocular pressure target must be individualized to the eye and revised at every visit. Prostaglandin analogues are the most effective medications and are recommended as the first choice in open-angle glaucoma (OAG). In patients with cataract and primary angle-closure glaucoma (PACG), phacoemulsification alone or combined phacoemulsification and glaucoma surgery are recommended. Trabeculectomy augmented with antifibrotic agents is recommended as the initial surgical treatment for OAG. Laser peripheral iridotomy and surgery in combination with medical treatment should be considered in high-risk individuals aged <50 years. In patients with phakic and PACG, phacoemulsification alone or combined phacoemulsification and glaucoma surgery are recommended. Visual acuity, VF testing, clinical assessment of the optic disc and RNFL, and tonometry are strongly recommended for monitoring glaucoma progression.

Exome sequencing and functional studies in zebrafish identify WDR8 as the causative gene for isolated Microspherophakia in Indian families.

Isolated Microspherophakia (MSP) is an autosomal recessive disorder characterized by a smaller than normal spherical lens. Till date, LTBP2 is the only gene shown to cause MSP. We used homozygosity mapping and whole-exome sequencing and identified a homozygous mutation, c.1148C > T (p.Pro383Leu), in the WDR8 (or WRAP73) gene in two Indian MSP families. In vitro experiments showed that the missense mutation renders the protein unstable. WDR8 is a centriolar protein that has important roles in centrosomal assembly, spindle pole formation and ciliogenesis. Co-immunoprecipitation experiments from HeLa cells indicated that the mutation interferes with the interaction of WDR8 with its binding partners. In zebrafish, both morpholino-mediated knockdown and CRISPR/Cas knockout of wdr8 resulted in decreased eye and lens size. The lack of wdr8 affected cell cycle progression in the retinal cells, causing a reduction in cell numbers in the retina and lens. The reduction in eye size and the cell cycle defects were rescued by exogenous expression of the human wild-type WDR8. However, the human mutant WDR8 (p.Pro383Leu) was unable to rescue the eye defects, indicating that the missense mutation abrogates WDR8 protein function. Thus, our zebrafish results suggested that WDR8 is the causative gene for MSP in these Indian families.

Uveitis, retinal vasculitis, and loss of accommodation as sole manifestations of demyelinating disease: A case report.

In this report we describe nongranulomatous uveitis followed by bilateral retinal vasculitis and much later by the loss of accommodation as initial presentations of demyelinating disease in a 42-year-old female with no other neurologic manifestations. The absence of demyelinating plaques in the initial magneric resonance imaging (MRI) (orbit and cranium) and its occurrence 2 years later, have been described as "lesions appearing with time". Extensive laboratory investigations ruled out infections, systemic vasculitis, and connective tissue disorders. Due to the presence of oligoclonal bands in both cerebrospinal fluid (CSF) and serum, absence of antiaquaporin-4, antimyelin-oligodendrocyte glycoprotein immunoglobulin G (IgG) antibodies, and negative vasculitis profile, the exact cause of demyelination (multiple sclerosis/vasculitis related) could not be ascertained. She has currently received 2 cycles of rituximab and at the last follow-up did not show any recurrences.

Older Drivers and Glaucoma in India: Driving Habits and Crash Risks.

PRéCIS:: In India, older drivers with glaucoma show greater driving difficulty but are not involved in higher number of on-road accidents. To achieve balance between safety aspects and independence for drivers with glaucoma is important. PURPOSE: The purpose of this study was to analyze driving habits of patients with glaucoma and to compare their driving behavior, driving difficulties, and accident rates with nonglaucoma controls. PATIENTS: Patients with glaucoma aged older than 40 years were recruited. Subjects with best-corrected visual acuity ≤6/24 in the better-seeing eye and those having primary eye disorder other than glaucoma were excluded. Age-matched nonglaucoma controls were recruited. Subjects with clinically significant cataract and/or with best-corrected visual acuity ≤6/24 in both eyes were excluded. All cases and controls were legally licensed to drive. MATERIALS AND METHODS: In this study, Driving Habits Questionnaire was used. Collected data were statistically analyzed using SAS, version 9.2 (GLM procedure), and IBM SPSS, version 22. P-values <0.05 were considered statistically significant. RESULTS: All controls and 84% (n=84/100) of cases were current drivers. Among them, 16% (n=16/100) cases had stopped driving, of which 31.25% (n=5/16) had stopped because of self-reported ocular causes. Cases drove lesser number of days per week (P=0.001) and had more driving dependence on other drivers (44%, n=37/84) compared with controls. Glaucoma was significantly associated with driving difficulty in the rain, in rush-hour traffic, and at night. Comparing driving difficulty scores and visual field index within glaucoma group showed statistical significance [F(1,82)=22.12, P<0.001]. Composite scores of driving difficulty (P<0.001) and driving space (P=0.003) between the 2 groups showed strong statistical significance. Controls had higher number of self-reported accidents (P<0.001). CONCLUSIONS: Patients with glaucoma show greater driving difficulty, self-regulate their driving behavior, and restrict their driving. Older patients with glaucoma in India are not involved in higher rates of on-road crash risks compared with nonglaucoma drivers.

Renewal of driving license in India and glaucoma: A study of prevalent practice and its lacunae.

PURPOSE: Glaucoma affects different aspects of vision including visual field. This prospective observational study aims to collect details of driving license (DL) renewal procedure (in an urban metro in India) among patients with diagnosed glaucoma and the method of reporting of vision-related requirements during renewal. METHODS: One-hundred patients with diagnosed glaucoma above 40 years, having valid DL (with at least one renewal cycle), were included. Patients with other ocular comorbidities were excluded. Driving Habits Questionnaire and a questionnaire about license renewal were administered. Driving eligibility was compared to international guidelines. RESULTS: Study population included patients with 69% early, 29% moderate, and 2% advanced glaucoma. Sixteen percent of patients had stopped driving. Legal license renewal procedure was bypassed by 45%. Form-1 was not submitted by 43% and 49% did not submit Form-1A at the time of renewal. Only 7.01% mentioned about glaucoma in the self-declaration form. None were asked about their visual field during renewal. Among 61 patients who submitted a medical certificate, the undersigning doctor was an ophthalmologist in only six patients. Thirty percent patients with valid Indian DL would not have satisfied International College of Ophthalmologists guidelines. Driving difficulties were experienced by 44%, more so in advanced glaucoma (F (1, 82) = 22.12, P < 0.001). CONCLUSION: Vision-related testing at the time of renewal of DL is inadequate in India. Chronic eye diseases such as glaucoma are commonly not self-declared or detected at pre-renewal testing. Clear-cut guidelines about visual requirements and implementation are required to prevent road traffic events because of vision-related errors.

Leveraging Digital Health Technologies and Outpatient Sampling in Clinical Drug Development: A Phase I Exploratory Study.

Merck & Co, Inc (Kenilworth, NJ) is investing in approaches to enrich clinical trial data and augment decision making through use of digital health technologies, outpatient sampling, and real-time data access. As part of this strategy, a phase I study was conducted to explore a few technologies of interest. In this fixed-sequence two-period trial, 16 healthy subjects were administered 50-mg once-daily sitagliptin packaged in a bottle that electronically captured the date and time study medication was dispensed (period 1) and in a traditional pharmacy bottle (period 2). Dried blood spot samples were collected for sitagliptin concentration analysis on select study days, both in clinic and at home, with collection time recorded using an electronic diary in period 1 and by clinic staff in period 2. Study results demonstrated the feasibility and subject acceptance of collecting digital adherence data and outpatient dried blood spot samples in clinical trials and highlighted areas for future improvements.

Femtosecond laser-assisted cataract surgery versus 2.2 mm clear corneal phacoemulsification.

PURPOSE: Phacoemulsification is the surgical procedure of choice for cataract, providing excellent visual and safety outcomes. Femtosecond laser-assisted cataract surgery (FLACS) is an addition to the surgical armamentarium. The study aims to compare the outcomes of FLACS using LenSx™ (Alcon Inc., USA) to standard 2.2 mm clear corneal phacoemulsification. Prospective case-control, comparative, interventional study was conducted in a tertiary care center. METHODS: In each group, 55 eyes of 55 patients underwent cataract surgery using either FLACS or conventional phacoemulsification (control group). The primary outcome variables, uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), specular microscopy, pachymetry, mean absolute error (MAE), and anterior chamber depth (ACD) were compared between two groups at 4 weeks postoperatively. Intraoperative effective phaco time (EPT), postoperative circularity of the rhexis, capsular overlap over the edge of the intraocular lens (IOL), and decentration of the IOL were the secondary variables which were compared. RESULTS: No significant difference was found between the groups for UCVA, pachymetry, MAE, and ACD at 4 weeks postoperatively. The FLACS group had better BCVA (P = 0.0294). Circularity of capsulorrhexis (P = 0), circular overlap over the edge of IOL (P = 0), and centration of IOL (P = 0.002) at 4 weeks postoperatively were better in the FLACS group. EPT was lower in FLACS for similar grade of cataract (P = 0). Endothelial cell loss in FLACS group was 4.2% more (P = 0.032). CONCLUSIONS: FLACS is superior to conventional phaco in the circularity of rhexis, capsular overlap, and centration of the IOL and uses less EPT. However, conventional phacoemulsification is equivalent to FLACS in most other parameters.

Cytomegalovirus anterior uveitis in immunocompetent individuals following topical prostaglandin analogues.

BACKGROUND: The aim of this study is to report two interesting cases of cytomegalovirus (CMV) anterior uveitis following topical prostaglandin analogue administration for glaucoma. Two retrospective case studies are presented. FINDINGS: A 40-year-old immunocompetent lady with a history of Fuchs heterochromic iridocyclitis with secondary glaucoma in the right eye since 2005 was diagnosed to have CMV anterior uveitis by a multiplex polymerase chain reaction (PCR) in 2009. She developed a reactivation of anterior uveitis following the addition of latanoprost 0.005% eye drops unknowingly by her local ophthalmologist. The pattern of endothelial deposits seen with this reactivation of uveitis was different from that seen in earlier or in subsequent reactivations. A 46-year-old immunocompetent lady with a history of primary open-angle glaucoma and no history of uveitis presented with anterior uveitis with medium-sized keratic precipitates following administration of travatoprost 0.004% eye drops. In both cases, the CMV antigen was demonstrated in the aqueous by multiplex PCR at the time of reactivation. Both cases required treatment with dexamethasone eye drops, ganciclovir 1% gel and oral valganciclovir for the control of inflammation along with antiglaucoma medications. CONCLUSIONS: We report two immunocompetent cases with the development of CMV-related anterior uveitis following administration with prostaglandin analogues. These cases increase the awareness of CMV anterior uveitis in immunocompetent individuals and the need to use prostaglandin analogues with caution.

Mobilizing pharmacogenomic analyses during clinical trials in drug development.

The utilization of pharmacogenomics (PGx) in drug development is increasing as pharmaceutical companies and regulatory agencies work to understand variation in response to medications. The implementation of PGx in clinical trials requires a number of considerations that begin early at the point of program development for a compound. This article will discuss the issues involved in mobilizing a PGx study during the conduct of a clinical trial, including the development of a PGx hypothesis, the identification of genetic markers for analysis, PGx platform selection and assay development, as well as challenges that arise in relation to global laws and regulations related to genetic research and logistical/timeline concerns in the execution of a PGx analysis.

Management of adult onset orbital hemangioma by oral propranalol: a case report.

Adult hemangiomas are usually benign vascular tumors presenting as painless progressive proptosis, sometimes accompanied by serious visual loss due to compression of the optic nerve. The current treatment modality for these hemangiomas is excision through orbitotomy. However, this may be associated with potentially serious side effects like injury to optic nerve, double vision, squint and ptosis. Many reports have been published demonstrating the impressive effect of systemic propranolol in the management of infantile hemangiomas. We report the successful use of systemic propranolol in a 56-year-old lady who had an extraconal apical orbital hemangioma, compressing the optic nerve. To our knowledge, this is the first reported case of adult onset hemangioma, resolving almost completely with oral propranolol treatment.

A homozygous mutation in LTBP2 causes isolated microspherophakia.

Microspherophakia is an autosomal-recessive congenital disorder characterized by small spherical lens. It may be isolated or occur as part of a hereditary systemic disorder, such as Marfan syndrome, autosomal dominant and recessive forms of Weill-Marchesani syndrome, autosomal dominant glaucoma-lens ectopia-microspherophakia-stiffness-shortness syndrome, autosomal dominant microspherophakia with hernia, and microspherophakia-metaphyseal dysplasia. The purpose of this study was to map and identify the gene for isolated microspherophakia in two consanguineous Indian families. Using a whole-genome linkage scan in one family, we identified a likely locus for microspherophakia (MSP1) on chromosome 14q24.1-q32.12 between markers D14S588 and D14S1050 in a physical distance of 22.76 Mb. The maximum multi-point lod score was 2.91 between markers D14S1020 and D14S606. The MSP1 candidate region harbors 110 reference genes. DNA sequence analysis of one of the genes, LTBP2, detected a homozygous duplication (insertion) mutation, c.5446dupC, in the last exon (exon 36) in affected family members. This homozygous mutation is predicted to elongate the LTBP2 protein by replacing the last 6 amino acids with 27 novel amino acids. Microspherophakia in the second family did not map to this locus, suggesting genetic heterogeneity. The present study suggests a role for LTBP2 in the structural stability of ciliary zonules, and growth and development of lens.

A study of the efficacy of endoscopic cyclophotocoagulation for the treatment of refractory glaucomas.

BACKGROUND: Endoscopic cyclophotocoagulation (ECP) is a relatively new method of cyclodestruction which can be used in the management of refractory glaucomas. AIM: To evaluate the safety and efficacy of ECP in the management of refractory glaucomas. SETTINGS AND DESIGN: Prospective interventional non-comparative study. MATERIALS AND METHODS: Fifty eyes of 50 patients with refractory glaucoma, whose intraocular pressures (IOP) were not under control with maximal medical therapy underwent ECP, by the anterior, or pars plana route. IOP, best corrected visual acuity (BCVA), and the number of anti-glaucoma medications, were compared postoperatively to preoperative values. Success was defined as IOP pound 22 mmhg, with or without use of medications. STATISTICAL ANALYSIS USED: Student's t test and repeated measures ANOVA were used to evaluate change in IOP and Student's t test, for comparison of BCVA. Kaplan Meier survival curve was plotted. Wilcoxon signed rank test was used to evaluate reduction in medications. RESULTS: Patients were followed for an average of 12.27 months (3-21months). IOP decreased significantly from 32.58 +/- 9.16 mmHg to 13.96 +/- 7.71 mmHg at last follow-up ( P < 0.001, student's t test). BCVA was significantly improved in the postoperative period ( P < 0.001, student's t test). The average number of antiglaucoma medications decreased from 2.51 +/- 0.97 to 1.09 +/- 1.16 ( P < 0.001, Wilcoxon signed rank test). ECP had a success rate of 82.2%. CONCLUSION: Endoscopic cyclophotocoagulation is an effective procedure in this subset of refractory glaucomas.