Next-generation sequencing-based genetic testing and phenotype correlation in retinitis pigmentosa patients from India

Purpose: Inherited retinal dystrophies (IRD) are a heterogeneous group of retinal diseases leading to progressive loss of photoreceptors through apoptosis. Retinitis pigmentosa (RP) is considered the most common form of IRD. Panel?based testing in RP has proven effective in identifying the causative genetic mutations in 70% and 80% of the patients. This is a retrospective, observational, single?center study of 107 RP patients who had undergone next?generation sequencing?based targeted gene panel testing for IRD genes. These patients were inspected for common phenotypic features to arrive at meaningful genotype–phenotype correlation. Methods: Patients underwent complete ophthalmic examination, and blood was collected from the proband for DNA extraction after documenting the pedigree. Targeted Next Generation Sequencing (NGS) was done by panel?based testing for IRD genes followed by co?segregation analysis wherever applicable. Results: Of the 107 patients, 72 patients had pathogenic mutations. The mean age of onset of symptoms was 14 ± 12 years (range: 5–55). Mean (Best Corrected Visual Acuity) BCVA was 6/48 (0.9 logMAR) (range 0.0–3.0). At presentation, over one?third of eyes had BCVA worse than 6/60 (<1 logMAR). Phenotype analysis with the gene defects showed overlapping features, such as peripheral well?defined chorioretinal atrophic patches in patients with CERKL, PROM1, and RPE65 gene mutations and large macular lesions in patients with RDH12 and CRX gene mutations, respectively. Nummular or clump?like pigmentation was noted in CRB1, TTC8, PDE6A, and PDE6B. Conclusion: NGS?based genetic testing can help clinicians to diagnose RP more accurately, and phenotypic correlations can also help in better patient counselling with respect to prognosis and guidance regarding ongoing newer gene?based therapies.

Anatomical and surgical considerations and outcomes in infantile Terson syndrome

Purpose: To study the presentation and outcomes of infantile Terson syndrome (TS). Methods: This was a retrospective analysis of 18 eyes of nine infants diagnosed to have TS?related intraocular hemorrhage (IOH). Results: Nine infants (seven males) were diagnosed to have IOH secondary to TS, of which eight infants had imaging features suggestive of intracranial bleed meeting our definite criteria. Median age at presentation was 5 months. In 11 eyes of six infants with suspected birth trauma, the median age of presentation was 4.5 months (range 1–5 months) of which one baby had a history of suction cup?aided delivery and four babies had a history of seizures. Vitreous hemorrhage (VH) was noted in 15 eyes (extensive in 11 eyes). Ten of these eyes showed membranous vitreous echoes, or triangular hyperechoic space with apex at the optic nerve head (ONH) posteriorly and base at the posterior lens capsule anteriorly, with or without dot echoes in the rest of the vitreous cavity, with a configuration of “tornado?like hemorrhage” suggestive of Cloquet’s canal hemorrhage (CCH). Eight eyes underwent lens?sparing vitrectomy (LSV) and one eye underwent lensectomy with vitrectomy (LV). On follow?up, disc pallor and retinal atrophy were noted in 11 and 10 eyes, respectively. The mean follow?up was 62 months (1.5 month–16 years). Visual acuity/behavior improved in all cases at the final follow?up. Developmental delay was noted in four children. Conclusion: Unexplained and altered vitreous hemorrhage with typical ultrasonography (USG) features should raise the suspicion of CCH in TS. Despite early intervention to clear visual axis, anatomical and visual behavior may remain subnormal.

Surgical management of complicated retinal detachment in a case of retinal hemangioblastoma

Background: A 40-year-old male presented with a complaint of sudden onset diminution of vision in the left eye for 2 weeks. He was a follow-up case with retinal hemangioblastoma in both eyes. He underwent two sittings of fundus fluorescein angiography-guided trans-pupillary thermotherapy 2 years back. Since then, he was regularly followed up for 2 years with stable vision and stable retinal findings. At present, the best-corrected visual acuity (BCVA) in the right eye is 6/6, and in the left eye, it is counting fingers 2 meters. On fundus examination, he had one active hemangioblastoma in the right eye and total retinal detachment in the left eye with multiple active lesions. The right eye was treated with a single sitting of thermotherapy, and the left eye underwent pars plana vitrectomy and angioma excision, followed by silicone oil tamponade. The immediate and late post?operative periods were uneventful, with successful anatomical and functional outcomes. The left eye BCVA on late follow-up was 6/36, no further treatment was advised, and the patient was kept under follow-up and observed closely. Purpose: To educate regarding the systemic workup, diagnosis, and surgical management of complicated retinal detachment in retinal hemangioblastoma. Synopsis: Systemic workup, diagnosis, and surgical steps in the management of complicated retinal detachment in retinal hemangioblastoma were performed. Highlights: Close follow-up, keen observation, and prompt treatment in the early stages of the disease are indispensable to prevent untoward sequelae of retinal hemangioblastoma. A thorough systemic workup is necessary to diagnose the systemic involvements early. Surgery, if indicated for the retinal hemangioblastoma or its associated sequelae, should be performed diligently and with careful handling of blood vessels and anomalous tissues.

Preferred practice patterns in aphakia management in adults in India: A survey

Purpose: To assess different approaches in the management of aphakia in adults in Indian ophthalmologists via an online survey. Methods: A survey-monkey based online questionnaire was fielded to Indian ophthalmologists in accordance with the CHERRIES guidelines. We recorded participants’ demographics, practice settings, and preferred surgical options including the type of intraocular lens (IOL) preferred when encountering a case of aphakia in adults with and without adequate capsular support. Differences between anterior segment (AS) surgeons and vitreoretinal (VR) surgeons as well as differences between surgeons with more or less than 10 years of surgical experience were evaluated using analytic statistics. Results: Of the 481 surgeons who responded to the survey, 369 (77%) were AS surgeons and the remaining 112 (23%) were VR surgeons and represented all regions of India. When encountering posterior capsular rent during cataract surgery, a three-piece IOL in the ciliary sulcus was the most preferred (n = 275, 57%) when there was adequate capsular support, while a retrofixated iris-claw IOL (n = 91, 19%) was the commonest choice in eyes without adequate capsular support. With associated nucleus drop, 85% of surgeons preferred to refer the patient to a VR surgeon and left the eye aphakic. Multivariable logistic regression showed that VR surgeons were more than six times likely to prefer a scleral fixated intraocular lens (SFIOLs) [odds ratio (OR) = 6.5, 95% confidence interval (CI) = 3.4–12.5, P < 0.001] and surgeons with >10 years of experience were also twice more likely to prefer an SFIOL (OR = 2.4, 95% CI = 1.2–4.9, P = 0.02). Conclusion: The choice of IOL in absence of capsular support in adult eyes differs between AS and VR surgeons and is also influenced by the surgeon’s experience.

Anterior staphyloma repair following trauma and surgery – A retrospective review of techniques and outcomes over 25 years

Purpose: To review surgical options, techniques, and outcomes of anterior staphyloma repair done following trauma and surgery. Methods: This was a retrospective case study of patients who underwent staphyloma repair with scleral or tibial periosteal patch grafts following trauma and surgery with a minimum follow-up of 3 months postoperatively. Preoperative risk factors, choice of graft materials, surgical details, and outcomes in terms of graft uptake and tectonic integrity were analyzed. Results: Seventeen eyes of 17 patients underwent successful staphyloma repair (scleral 15, tibial periosteal two). Mean follow-up was 47.1 months (3–159 months). Postoperative intraocular pressure rise noted in four eyes was controlled medically or surgically. Three patients underwent successful repeat patch grafting (graft melt one and recurrent ectasia two). Tectonic integrity of the eyeball was restored and maintained in all patients at the final follow-up. Conclusion: Comprehensive evaluation of the risk factors, control of ocular comorbid conditions, and early and meticulous surgery can optimize results.

Genetic testing in four Indian families with suspected Stickler syndrome

Purpose: Stickler syndrome is associated with the development of rhegmatogenous retinal detachment (RRD), and often presents with ocular, auditory, skeletal, and orofacial abnormalities. Molecular analysis has proven effective in diagnosis, confirmation and classification of the disease. We aimed to describe the utility of next?generation sequencing (NGS) in genetic analysis of four Indian families with suspected Stickler syndrome. Methods: The index cases presented with retinal detachment with family history. Genetic analysis in the index case was performed by next?generation sequencing of inherited retinal degeneration genes, and validated by Sanger sequencing followed by co?segregation analysis in the other family members. Results: Twenty patients were included for the genetic analysis (15 males and 5 females from four families). Clinical details were available for 15 patients (30 eyes). Fourteen eyes (11 patients) developed RRD. In the 16 eyes without RRD, 8 underwent barrage laser to lattice degeneration and 8 were under observation. Disease segregating heterozygous mutations with pathogenic/likely pathogenic effect was identified in COL2A1 (c.4318?1G>A, c.141G>A, c.1221+1G>A for 3 families) and COL11A1 (c.1737+1 G>A for 1 family) gene. In addition to the mutation in the COL2A1 gene, a pathogenic heterozygous variant associated with risk for arrhythmogenic right ventricular cardiomyopathy (ARVC) was identified in one member. Conclusion: NGS testing confirmed the presence of the causative gene for Stickler syndrome in the index case followed by evaluation of family members and confirmation of genetic and ocular findings. We believe that this may be the first such report of families with RRD from India

Outcomes of macular buckling with a T-shaped buckle for myopic tractional maculopathies associated with posterior staphyloma: An Indian experience

Purpose: To report the anatomic and visual outcomes following macular buckling in patients affected by pathological myopia?associated foveoschisis (FS) and macular detachment with or without macular hole (MH). Methods: A retrospective interventional consecutive case series wherein 25 highly myopic eyes (mean axial length 28.46 mm; range, 25–33.8 mm) of 24 patients (16 females and 8 males; mean age 54.1 years; range, 35–74 years) presenting with macular detachment associated with a posterior staphyloma (PS), who underwent macular buckling, were evaluated. Patients with absence or reduction in subretinal fluid by more than 90% during the final follow?up along with inversion of contour of staphyloma were considered to have a successful anatomical outcome and those with improvement or maintenance in visual acuity were considered to have a successful functional outcome. The mean duration of follow?up was 11.2 months. Results: At the time of initial presentation, the mean age of the 24 patients was 54.1 ± 10.28 years. Macular detachment along with FS was present in all cases, whereas full?thickness macular hole?related retinal detachment was present in nine cases. Swept?source optical coherence tomography parameters showed reduction of FS with foveal reattachment in all eyes except one at last visit. Mean axial length decreased from 28.5 mm preoperatively (range 26–33.8 mm) to 26.2 mm (range 24–29.3 mm). The mean best?corrected visual acuity changed from 1.16 log MAR to 1.096 Log MAR (P = 0.165). Visual acuity improved in 10 eyes (40%), remained stable in 11 eyes (44%) and decreased in 4 eyes (16%). Conclusion: Macular buckling is a good surgical technique with encouraging anatomic and visual outcomes in patients with myopic macular detachment associated with PS. Highly selective cases of myopic traction maculopathy can have a viable option of macular buckle surgery in stabilizing the retinal tractional changes, and thereby, vision loss.

Linguatula serrata in the anterior chamber of the eye.

We report a case of intraocular Linguatula in healthy young female who presented with a history of trivial trauma, dislocated lens, inflammation and secondary glaucoma. A mobile worm was seen in the anterior chamber. Pars plana lensectomy and vitrectomy was planned to remove both the cataractous lens and the parasite during which the worm disappeared from view but was later recovered from the cassette fluid. It was identified as the nymphal form of Linguatula serrata (tongue worm).

Brachytherapy of intra ocular tumors using ‘BARC I-125 Ocu-Prosta seeds’: An Indian experience.

Aim: To report our experience of brachytherapy using ‘BARC I‑125 Ocu‑Prosta seeds’ for the management of intraocular tumors with regard to tumor control, globe preservation visual outcome, and patient survival at Sankara Nethralaya, Chennai, India between September 2003 and May 2011. Materials and Methods: We reviewed records of 35 eyes of 35 patients who underwent ophthalmic brachytherapy between September 2003 and May 2011. Twenty‑one cases had choroidal melanoma, nine had childhood retinoblastoma, two had adult‑onset retinoblastoma, and there were one case each of vasoproliferative tumor, retinal angioma, and ciliary body melanoma. Brachytherapy was administered using a 15‑ or 20‑mm gold plaque with or without a notch. Brachytherapy was the primary treatment modality in all tumors other than retinoblastoma, wherein brachytherapy was done post chemoreduction for residual tumor. Results: For choroidal melanomas, the mean radiation dose was 68.69 ± 15.07 (range, 47.72-94.2) Gy. The eye salvage rate was 13/20 (65%) and tumor control rate was 16/20 (80%) at an average follow‑up of 24.43 ± 24.75 (range, 1.5-87.98) months. For retinoblastoma, the mean dose was 45.85 ± 3.90 (range, 39.51-50.92) Gy. The eye salvage rate and tumor control rate was 5/6 (83.3%) at an average follow‑up of 38.36 ± 31.33 (range, 4.14-97.78) months. All eyes with retinoblastoma needed additional focal therapy for tumor control and eye salvage. Conclusion: The results of this retrospective study confirms that the use of ‘BARC I‑125 Ocu‑Prosta seeds’ in episcleral plaques to treat intraocular tumors offers a viable option for the management of intraocular cancers.

Choroidal neovascularization associated with coloboma of the choroid: A series of three cases.

Choroidal neovascularization (CNV) is a rare complication associated with coloboma of the choroid. We describe three cases of coloboma choroid where there was loss of vision due to CNV development at the edge of the coloboma. One was managed by photodynamic therapy alone and two were managed by a combination of reduced fluence PDT and intravitreal bevacizumab. Significantly we noted that one treatment session was sufficient to achieve regression of the CNV and improvement in visual acuity.

Coats' disease: An Indian perspective.

Aim: To describe the clinical features, treatment and outcome patterns in 307 eyes with Coats' disease. Materials and Methods: Retrospective chart review of patients diagnosed with Coats' disease between January 1996 and January 2006 from a single referral center in southern India. Results: Two hundred and eighty patients (307 eyes) with mean age of 15.67 years (range: Four months-80 years) were included. Decreased vision (77%), unilateral affection (90%) and male preponderance (83.4%) were chief presenting features. Anterior segment involvement was seen in 67 (21.8%) eyes. Retinal telangiectasia were seen in 302 (99%) eyes, exudation in 274 (89%) eyes and retinal detachment in 158 (51.5%) eyes. Four-quadrant disease was seen in 207 (67.2 %) eyes. Visual acuity was < 20/200 in 249 (80.9%) eyes. One hundred and nine of 176 treated eyes (61.93%) had favorable anatomical outcome; 207 of 280 eyes (74%) had an optimal structural outcome. Seventeen (5.3%) eyes were enucleated. Complications following treatment included phthisis bulbi (7%), neovascular glaucoma (5%), epiretinal membrane (4.4%) and rubeosis iridis (4.4%). Conclusion: Indian patients with Coats' disease have a high male predominance, the majority of whom present with severe visual impairment and extensive four-quadrant exudation. Unusual presentations such as pain, vitreous hemorrhage and a high incidence of anterior segment involvement are distinctive to Indian eyes.

Functional and anatomical outcomes after primary lens-sparing pars plana vitrectomy for Stage 4 retinopathy of prematurity.

Background: While lens-sacrificing vitrectomy is the standard approach to manage Stage 5 retinopathy of prematurity (ROP), scleral buckling has been used to manage some cases of Stage 4. Lens-sparing vitrectomy was popularized by Maguire and Trese in selected cases of Stage 4 disease. Purpose: To assess the functional and visual outcomes after primary lens-sparing pars plana vitrectomy for Stage 4 ROP. Materials and Methods: In a retrospective, interventional, consecutive case series, the records of 39 eyes of 31 patients presenting with Stage 4 retinal detachment secondary to ROP who underwent primary two or three-port lens-sparing vitrectomy from January 2000 to October 2006 were evaluated. The outcomes studied at the final follow-up visit were the retinal status, lens and medial clarity and visual acuity. Favorable anatomical outcome was defined as the retinal reattachment of the posterior pole at two months after the surgery; and favorable functional outcome was defined as a central, steady and maintained fixation, with the child following light. Results: At mean follow-up of 15 months, 74% of the eyes had a favorable anatomical outcome with single procedure. The visual status was favorable in 63%. The lens remained clear in all the eyes at the last follow-up, and the media clarity was maintained in 87%. Intraoperative complications included vitreous hemorrhage, pre-retinal hemorrhage and retinal break formation. Conclusions: Lens-sparing vitrectomy helps to achieve a favorable anatomical and functional outcome in selected cases of Stage 4 ROP.

Endophthalmitis caused by Acinetobacter calcoaceticus. A profile.

PURPOSE: To report the clinical and microbiological profile of endophthalmitis caused by Acinetobacter calcoaceticus. METHODS: A retrospective study of case series of Acinetobacter calcoaceticus endophthalmitis. Outcome measures included ability to sterilise the eye, anatomical result (clear media and attached retina) and visual recovery (visual acuity > 6/60). RESULTS: Of the 20 cases studied, 10 were cases of postoperative endophthalmitis, 3 were posttraumatic, 6 were endogenous and one was bleb-related endophthalmitis. Specific features of interest observed were relative chronicity of presentation and absence of any obvious predisposing factor in endogenous endophthalmitis cases. All cases could be sterilised except one, which needed evisceration. Cases with postoperative endophthalmitis had better anatomical outcome (7/10 with attached retina and clear media) and visual outcome (4/10 regained vision > 6/18). Higher smear positivity was seen in vitreous samples (72.2%) compared to aqueous samples (37.5%). Culture positivity was higher from the vitreous cavity compared to aqueous. The organism was sensitive to ciprofloxacin in a high percentage (88.9%) of cases. CONCLUSIONS: Visual recovery in Acinetobacter calcoaceticus endophthalmitis is modest. Ciprofloxacin is the antibiotic of choice.