Parveen Sen

Intravitreal voriconazole for drug-resistant fungal endophthalmitis: case series.

Purpose: To report the efficacy of intravitreal voriconazole. Methods: Retrospective analysis of an interventional case series of five cases of culture-proven fungal endophthalmitis treated with intravitreal voriconazole was done. Only cases found to be resistant to conventional antifungal agents were included in the study. The diagnosis of fungal endophthalmitis was established on the basis of clinical as well as microbiological examination. All patients received one or more intravitreal injections of voriconazole. Resolution was determined on the basis of clinical examination. Resolution of infection and final visual acuity were the main outcome measures. Results: Resolution of infection was achieved in all five cases. Visual acuity was better in three cases and was maintained in two. Of the three patients who had improvement, two had vision better than or equal to 20/120. Evisceration was avoided in one case with maximal antifungal treatment including voriconazole. Conclusions: Voriconazole definitely adds to the available treatment options for fungal endophthalmitis. Because of its broad spectrum of activity, it is efficacious in even amphotericin–B– and fluconazole-resistant fungal endophthalmitis.

A 32 kb critical region excluding Y402H in CFH mediates risk for age-related macular degeneration

Complement factor H shows very strong association with Age-related Macular Degeneration (AMD), and recent data suggest that multiple causal variants are associated with disease. To refine the location of the disease associated variants, we characterized in detail the structural variation at CFH and its paralogs, including two copy number polymorphisms (CNP), CNP147 and CNP148, and several rare deletions and duplications. Examination of 34 AMD-enriched extended families (N = 293) and AMD cases (White N = 4210 Indian = 134; Malay = 140) and controls (White N = 3229; Indian = 117; Malay = 2390) demonstrated that deletion CNP148 was protective against AMD, independent of SNPs at CFH. Regression analysis of seven common haplotypes showed three haplotypes, H1, H6 and H7, as conferring risk for AMD development. Being the most common haplotype H1 confers the greatest risk by increasing the odds of AMD by 2.75-fold (95% CI = [2.51, 3.01]; p = 8.31×10−109); Caucasian (H6) and Indian-specific (H7) recombinant haplotypes increase the odds of AMD by 1.85-fold (p = 3.52×10−9) and by 15.57-fold (P = 0.007), respectively. We identified a 32-kb region downstream of Y402H (rs1061170), shared by all three risk haplotypes, suggesting that this region may be critical for AMD development. Further analysis showed that two SNPs within the 32 kb block, rs1329428 and rs203687, optimally explain disease association. rs1329428 resides in 20 kb unique sequence block, but rs203687 resides in a 12 kb block that is 89% similar to a noncoding region contained in ΔCNP148. We conclude that causal variation in this region potentially encompasses both regulatory effects at single markers and copy number.

Prevalence of idiopathic macular hole in adult rural and urban south Indian population

Background:  This study was undertaken to evaluate the prevalence of idiopathic macular hole in a defined community in Southern India.

Prevalence of Retinitis Pigmentosa in South Indian Population Aged Above 40 Years

Purpose: The study was undertaken to evaluate the prevalence of retinitis pigmentosa (RP) in rural and urban South India. Methods: Seven thousand seven hundred and seventy four subjects aged 40 years or more from rural and urban Tamil Nadu, underwent comprehensive ophthalmic examination out of 9576 enumerated (81.17%). After a thorough ophthalmic examination, fundus photographs were taken for documentation. Statistical analysis was done using SPSS for Windows (ver 14). Results: 7461 (95.9%) subjects had fundus details seen in both eyes. Thirteen subjects (0.17%; 4 males, 9 females) were diagnosed as retinitis pigmentosa. Retinitis pigmentosa in the urban population was seen in approximately 1 in 930 persons, while 1 in 372 of rural subjects had the disorder. This figure is greater than other reports from the western populations and that of the conservative estimate of 1 in 4000. The age and gender adjusted prevalence rate of retinitis pigmentosa to national census 2001 was 0.155%. Eight subjects (61.53%) had visual acuity less than 3/60. Conclusion: Prevalence of RP in South India appears to be alarmingly higher in comparison to those seen in other parts of the world.

Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families

Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP) south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s) in the homozygous block identified mutations in ten families; AIPL1 – 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60%) mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier.

Multifocal visual evoked potential in optic neuritis, ischemic optic neuropathy and compressive optic neuropathy.

Purpose: To investigate the effect of optic neuritis (ON), ischemic optic neuropathy (ION) and compressive optic neuropathy (CON) on multifocal visual evoked potential (mfVEP) amplitudes and latencies, and to compare the parameters among three optic nerve disorders. Materials and Methods: mfVEP was recorded for 71 eyes of controls and 48 eyes of optic nerve disorders with subgroups of optic neuritis (ON, n = 21 eyes), ischemic optic neuropathy (ION, n = 14 eyes), and compressive optic neuropathy (CON, n = 13 eyes). The size of defect in mfVEP amplitude probability plots and relative latency plots were analyzed. The pattern of the defect in amplitude probability plot was classified according to the visual field profile of optic neuritis treatment trail (ONTT). Results: Median of mfVEP amplitude (log SNR) averaged across 60 sectors were reduced in ON (0.17 (0.13-0.33)), ION (0.14 (0.12-0.21)) and CON (0.21 (0.14-0.30)) when compared to controls. The median mfVEP relative latencies compared to controls were significantly prolonged in ON and CON group of 10.53 (2.62-15.50) ms and 5.73 (2.67-14.14) ms respectively compared to ION group (2.06 (-4.09-13.02)). The common mfVEP amplitude defects observed in probability plots were diffuse pattern in ON, inferior altitudinal defect in ION and temporal hemianopia in CON eyes. Conclusions: Optic nerve disorders cause reduction in mfVEP amplitudes. The extent of delayed latency noted in ischemic optic neuropathy was significantly lesser compared to subjects with optic neuritis and compressive optic neuropathy. mfVEP amplitudes can be used to objectively assess the topography of the visual field defect.

Photodynamic monotherapy or combination treatment with intravitreal triamcinolone acetonide, bevacizumab or ranibizumab for choroidal neovascularization associated with pathological myopia.

This retrospective, interventional case series analyses treatment outcomes in eyes with choroidal neovascularization (CNV) secondary to pathological myopia, managed with photodynamic therapy, (PDT), (Group 1, N = 11), PDT and intravitreal triamcinolone acetonide (4 mg/0.1ml) (Group 2, N = 3), PDT and intravitreal anti-vascular endothelial growth factor (anti-VEGF) bevacizumab 1.25 mg/0.05 ml, ranibizumab 0.5 mg/0.05 ml and reduced-fluence PDT and intravitreal ranibizumab 0.5 mg/0.05 ml (Group 3, N=12). All the patients underwent PDT. Intravitreal injections were repeated as required. SPSS 14 software was used to evaluate the data. Wilcoxon signed ranks test was used to evaluate pre- and post-treatment vision. The Kruskal-Wallis test was used for comparison between the groups. All the groups were statistically comparable. All the eyes showed complete regression of CNV, with a minimum follow-up of six months. All groups had visual improvement; significantly in Group 3 (P = 0.003). Combination PDT with anti-VEGF agents appeared to be efficacious in eyes with myopic CNV. However, a larger study with a longer follow-up is required to validate these results.

Next-generation sequencing confirms the implication of SLC24A1 in autosomal-recessive congenital stationary night blindness

Congenital stationary night blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder which represents rod photoreceptor dysfunction or signal transmission defect from photoreceptors to adjacent bipolar cells. Patients displaying photoreceptor dysfunction show a Riggs‐electroretinogram (ERG) while patients with a signal transmission defect show a Schubert–Bornschein ERG. The latter group is subdivided into complete or incomplete (ic) CSNB. Only few CSNB cases with Riggs‐ERG and only one family with a disease‐causing variant in SLC24A1 have been reported. Whole‐exome sequencing (WES) in a previously diagnosed icCSNB patient identified a homozygous nonsense variant in SLC24A1. Indeed, re‐investigation of the clinical data corrected the diagnosis to Riggs‐form of CSNB. Targeted next‐generation sequencing (NGS) identified compound heterozygous deletions and a homozygous missense variant in SLC24A1 in two other patients, respectively. ERG abnormalities varied in these three cases but all patients had normal visual acuity, no myopia or nystagmus, unlike in Schubert–Bornschein‐type of CSNB. This confirms that SLC24A1 defects lead to CSNB and outlines phenotype/genotype correlations in CSNB subtypes. In case of unclear clinical characteristics, NGS techniques are helpful to clarify the diagnosis.

Long-term results of intravitreal ranibizumab for osteoma-related choroidal neovascularization in a child

Though choroidal osteoma is a rare benign tumor, associated choroidal neovascularization (CNV) can be a cause of severe visual loss. A nine-year-old boy presented with one-month history of decreased vision in left eye. Upon a complete ophthalmologic examination, including fundus fluorescein angiography and optical coherence tomography, he was diagnosed with choroidal osteoma-related subfoveal CNV in the left eye. The CNV was associated with subretinal hemorrhage, subretinal fluid, and cystoid macular edema. Owing to the young age and subfoveal localization of the CNV, intravitreal ranibizumab injection was performed on this patient after a detailed discussion with the parents of its safety profile. No local or systemic complications were noted. No recurrence of CNV lesion was noted during 30 months of follow-up, and the vision was maintained. This report shows the favorable outcome of intravitreal injection of ranibizumab in choroidal osteoma-related CNV in a child.

Electrophysiological findings in Bietti's crystalline dystrophy

Purpose:  The aim was to investigate multifocal electroretinogram (mfERG) findings in Biettis crystalline dystrophy (BCD) using a retrospective, non‐interventional, consecutive case series.