Varun Chaudhary

Re-operation of idiopathic full-thickness macular holes after initial surgery with internal limiting membrane peel

Background/aims A retrospective consecutive case series to evaluate the efficacy of re-operation in patients with persistent or recurrent idiopathic full-thickness macular hole after initial surgery with internal limiting membrane peel (ILM). Methods 491 patients underwent surgery for full-thickness macular hole from January 2004 to November 2007. Fifty-five patients either did not close or reopened during the follow-up period. Thirty patients with initial ILM peel underwent repeat surgery involving vitrectomy, enlargement of ILM rhexis and gas tamponade. Results Anatomical closure rate was 88.8% for primary surgery and 46.7% (14/30) for re-operation. There was a statistically significant improvement in overall best corrected visual acuity (BCVA) from re-operation baseline BCVA (p=0.02) within 1 year. For holes that did not close after the second surgery, visual acuity did not worsen. Conclusion Re-operation has a reduced success rate of anatomical closure. However, BCVA is statistically significantly improved from re-operation baseline, so even though we cannot return vision to pre-pathological baseline, re-operation can improve on this new baseline.

Extracellular Matrix Proteins in Epiretinal Membranes and in Diabetic Retinopathy

Purpose: Non-vascular epiretinal membranes (ERM) and neovascular membrane in proliferative diabetic retinopathy (PDR) are recognized causes of visual impairment. Both ERMs and neovascular membranes in PDR consist of cellular components and extracellular matrix (ECM) proteins such as fibronectin (FN) and collagen. Transforming growth factor-β (TGF-β) and endothelin-1 (ET-1) regulate ECM protein production. In this study, we investigated ECM proteins and their regulators in ERMs and vitreous from PDR subjects and non-diabetic subjects undergoing vitrectomy. Methods: ERMs from non-diabetic subjects undergoing membrane peeling were collected. Vitreous samples from non-diabetic and PDR subjects undergoing vitrectomy were also collected and separated into solid pellets consisting of fibrovascular tissue and vitreous fluid. Real-time PCR was done for estimating mRNA levels of extracellular matrix proteins like collagen, FN, its splice variant extra-domain B containing FN (EDBFN), and their regulators, TGF-β and ET-1. ELISA was done to detect the EDBFN level in blood and vitreous from non-diabetic and PDR subjects undergoing vitrectomy. Results: ECM proteins, including FN, its splice variant EDBFN, and collagen were significantly upregulated in the ERMs and PDR compared to vitreous from both other two group. The levels were, however, higher in the ERM. ECM protein regulators like TGF-β and ET-1 were also elevated. FN and EDBFN show significant correlation with TGF-β in vitreous but not in ERMs. Plasma and vitreous EDBFN were elevated in the PDR subjects compared to non-diabetic subjects. Conclusions: Data from these studies show that ECM proteins such as EDBFN and collagen are upregulated in ERM and PDR, and are regulated by TGF-β. Elevated serum EDBFN in the PDR may potentially be further explored as a possible molecular marker for the early detection of diabetic end organ damages.

Incidence of retinopathy of prematurity and risk factors among premature infants at a neonatal intensive care unit in Canada.

PURPOSE To study the incidence of retinopathy of prematurity (ROP) in a neonatal intensive care unit and obtain information on risk factors associated with ROP. METHODS Four hundred twenty-three infants were screened for ROP between July 2006 and July 2010. Demographic information, clinical data, and risk factors were reviewed. RESULTS The incidence was 40.4% (171 infants) for ROP, 9.2% (39 infants) for severe ROP, and 5.67% (24 infants) for laser treatment. Mean gestational age and birth weight were significantly lower among infants with ROP versus those without ROP (26 ± 0.13 vs 28.55 ± 0.12 weeks, P < .0001 and 840.5 ±17.49 vs 1,190.24 ± 20.20 g, P < .0001, respectively). Birth weight (P < .001), gestational age (P < .001), mechanical ventilation therapy (P = .039), and necrotizing enterocolitis (P = .019) were independent risk factors for ROP. CONCLUSION Gestational age and birth weight were the most significant risk factors for developing ROP. The study population had an elevated percentage of infants with birth weight less than 1,000 g (extremely low birth weight), yet there was no corresponding increase in severe ROP incidence and treatment when compared to other studies.

Effects of telazol and nembutal on retinal responses

Purpose: Compare the effects of Nembutal, a barbiturate, and Telazol, a dissociative anesthetic, on photoreceptor and post-receptoral retinal responses. Methods: Dark adapted infant and adult albino rats were anesthetized with intraperitoneal injection of Nembutal or Telazol. ERG responses to full-field stimuli were recorded over a 6–8 log unit range from dim intensities at which the scotopic threshold response (STR) was observed to those that saturate the a-wave. The rod photoresponse, b-wave, oscillatory potentials (OPs), and STR parameters of rats in the Nembutal and Telazol groups were compared. Results: For both infants and adults, the saturated amplitudes of the photoresponse and the b-wave were larger in Telazol than Nembutal rats, but sensitivity of the photoresponse did not differ significantly between Telazol and Nembutal rats. The STR was seen only in the Telazol responses of adults. There was little differential effect of the two agents on the OPs. Conclusions: Photoreceptor and postreceptoral responses recorded under Nembutal and Telazol anesthesia differ significantly. These results may inform selection of anesthetic for studies of animal models.

Ozurdex in age-related macular degeneration as adjunct to ranibizumab (The OARA Study)

OBJECTIVE To evaluate the utility of dexamethasone intravitreal implant (DXI; Ozurdex; Allergan, Irvine, Calif.) in combination with ranibizumab (Lucentis; Novartis Pharma AG, Basel, Switzerland) versus ranibizumab monotherapy on visual acuity (VA) and anatomical outcomes in a neovascular age-related macular degeneration (nAMD) cohort. DESIGN Multicentred, single-blinded, pilot randomized control trial. PARTICIPANTS Ten patients 50 years or older with subfoveal choroidal neovascularization secondary to AMD were randomized to receive DXI in combination with ranibizumab (group 1) or ranibizumab alone (group 2) after a 3-month ranibizumab loading period. METHODS Group 1 patients received 1 DXI after the loading phase with the option of retreatment at months 4 to 6. Ranibizumab was administered pro re nata for 6 months in both study arms. Mean VA and central macular thickness (CMT) reductions from baseline to study endpoint (9 months) were reported in addition to adverse event frequency across study cohorts. RESULTS From baseline to the study endpoint, VA improved by 10.8 ± 13.2 Early Treatment of Diabetic Retinopathy Study letters in the control arm and 3.0 ± 10.5 letters in the intervention arm (p = 0.331). CMT decreased by 31.7% ± 17.5% and 13.3% ± 27.0% (p = 0.236) for the control and intervention cohorts, respectively. One patient developed intraocular pressure in excess of 30 mm Hg 3 months after DXI administration. CONCLUSIONS For this nAMD population, no visual or anatomical benefits were observed when treating with DXI in adjunct to ranibizumab relative to ranibizumab monotherapy. DXI-related adverse events were consistent with those previously documented for dexamethasone.

Discrepancies in physician–patient agreement in reporting ocular history

OBJECTIVE The purpose of this study was to investigate the extent of agreement between physicians and patients in reporting ocular history and to determine whether there are any predictive factors for physician-patient consensus. DESIGN Retrospective chart review. PARTICIPANTS Between June and September 2014, adult patients undergoing cataract surgery were recruited for the study. METHODS Before surgery, patient demographics and self-reported ocular history were extracted from a prospectively collected database. Medical charts were retrospectively examined to retrieve physician-reported ocular history. RESULTS One hundred and thirty-eight patients participated. Mean cohort logMAR visual acuity was 0.46 ± 0.34 (Snellen equivalent of approximately 20/60) and mean age was 74.1 ± 8.3 years. For glaucoma, Cohens kappa revealed a moderate-to-good concordance between physicians and patients (κ = 0.604), whereas a poor-to-fair level of agreement existed in reporting maculopathy, such as age-related macular degeneration and macular holes (κ = 0.254). The logistic regression model revealed that preoperative visual acuity (p = 0.223), sex (p = 0.736), age (p = 0.910), and education (p = 0.738) were not significant predictors of physician-patient agreement. CONCLUSIONS The accuracy of patient-reported ocular history varies by pathology. Self-reported glaucoma history is consistent between patients and physicians; however, patients under-report the diagnosis of maculopathy. Age, sex, and level of education do not appear to influence patient-reported accuracy of ocular comorbidities.

Genetic Risk Evaluation in Wet Age-Related Macular Degeneration Treatment Response.

Objective: To evaluate the pharmacogenetic relationship between CFH haplotypes and single nucleotide polymorphisms (SNPs) with response to ranibizumab treatment for neovascular age-related macular degeneration (nAMD). Patients and Methods: This was a prospective cohort study involving 70 treatment-naive nAMD patients. Patients were genotyped for CFH haplotypes and SNPs in the C3, ARMS2, and mtDNA genes. Visual acuity and central macular thickness were assessed at baseline and during 6 monthly follow-up visits. Multivariate logistic regression was used to determine the association between genotypes and a gain of ≥15 letters at the 6-month endpoint after adjusting for potential confounders. Results:CFH haplotypes were associated with a gain of ≥15 letters at the 6-month endpoint (p = 0.046). Patients expressing protective haplotypes were more likely to achieve a gain of ≥15 letters relative to the greatly increased risk haplotypes [OR 6.58 (95% CI: 1.37, 31.59)]. Conclusion:CFH is implicated in nAMD patient treatment response to ranibizumab.

Predictors of functional vision changes after cataract surgery: the PROVISION study

OBJECTIVE To ascertain whether time-to-treatment, sex, age, preoperative functional vision scores, education, and ocular comorbidities predict change in functional vision pre- to postoperatively in patients receiving cataract surgery. DESIGN Prospective cohort study. PARTICIPANTS Three hundred and forty-three cataract patients at the Hamilton Regional Eye Institute. METHODS Participants 18 years or older scheduled to undergo cataract surgery completed the Catquest-9SF functional vision questionnaire on the day of their surgery and were mailed a survey 2-3 months postoperatively. Multivariate linear regression was used to determine the ability of predictors to explain variability in functional vision change between questionnaire administrations. RESULTS One hundred and sixty-six patients completed both baseline and follow-up questionnaires. Mean age of the cohort was 73.8 ± 8.1 years. Most patients were female (59.6%), had cataract surgery performed for the first time (66.9%), and had spent a mean time of 20.3 ± 20.7 weeks waiting for surgery. Functional vision improved in 83.7% of patients. The mean baseline Catquest-9SF score was the only significant predictor of functional vision improvement (adjusted R(2) = 0.47; F1,159 = 144.6; p < 0.001). Controlling for other variables, functional vision improved by 0.74 logits when mean baseline survey score increased by 1 logit. CONCLUSIONS In most patients, functional vision improved after cataract surgery. Mean baseline Catquest-9SF score was a moderate predictor of the observed improvement.

Waiting room educational media effect on preinjection anxiety for initial intravitreal injections

OBJECTIVE To ascertain the effectiveness of an educational web page in reducing anxiety associated with initial intravitreal anti-vascular endothelial growth factor injections. DESIGN Single-centred, observation-enriched, randomized controlled trial. PARTICIPANTS Ninety-six patients receiving intravitreal injections at the Hamilton Regional Eye Institute. METHODS Patients aged 18 years or older scheduled to receive their first intravitreal injection were randomized to either view an educational web page pertaining to the injection procedure or wait 30 minutes. Both groups then completed the State-Trait Anxiety Inventory (STAI). A third cohort of patients who previously had intravitreal injections waited 30 minutes before completing the STAI. The difference between STAI anxiety scores across cohorts 1 through 3 was assessed using analysis of variance and independent t tests where applicable. RESULTS Ninety-six patients completed the STAI questionnaires, of which 55 (57.3%) were female and 86 (89.6%) were Caucasian. The mean age of participants was 68.5 ± 14.2 years, 72.7 ± 12.9 years, and 70.4 ± 11.7 years for control, intervention, and treatment-experienced cohorts, respectively. The mean STAI score was 40.3 ± 12.0 for the control cohort, 39.3 ± 11.1 for the intervention cohort, and 30.2 ± 9.9 for the treatment-experienced cohort. No significant difference in STAI scores was observed between intervention and control cohorts (p = 0.716). The effect size between treatment-naïve and treatment-experienced cohorts was high, ranging from 0.862 and 0.919, and the mean difference in STAI scores was significant. CONCLUSIONS Compared to treatment-experienced patients, treatment-naïve patients are more anxious. Electronic educational information about the intravitreal injection process may be ineffective at reducing procedure-induced anxiety.

Genetic Risk Factors Are Not Associated with Wet Age-Related Macular Degeneration Treatment Response to Ranibizumab

patients who withdrew differed from the 12-month cohort in having a worse VA by an average of 12 letters (p = 0.0012). Univariate analysis suggested no association between any genotyped markers with respect to VA or central macular thickness. Consistent with the 6-month findings, 66.7% of patients expressing reduced-risk CFH haplotypes gained ≥15 letters after 1 year. 46.9% of increased-risk and greatly increased-risk haplotype-expressing patients had gained ≥15 letters at 1 year compared to 27.6% of patients at 6-months. The 12-month study extension findings suffer from a number of limitations. Namely, the study was underpowered to detect the differences observed in the proportion of patients gaining ≥15 letters by haplotype. In addition, participants who withdrew following the 6-month endpoint had poorer VA outcomes compared to the remaining study population. 90% of dropouts expressed CFH risk haplotypes. Pharmacogenetic response to ranibizumab treatment in the CFH reduced-risk haplotype cohort remained stable from 6 months to 12 months. Two-thirds of patients in this cohort experienced vision gains of ≥15 letters. Despite this, the statistically significant association between CFH reduced-risk haplotype-expressing patients having proportionally more individuals Dear Editor, We previously reported an association between CFH haplotypes and ranibizumab treatment response [1] wherein CFH reduced-risk haplotypes were associated with a ≥15 Early Treatment of Diabetic Retinopathy Study letter gain at a 6-month endpoint in a cohort of 70 treatment-naïve wet age-related macular degeneration (AMD) patients. Following the primary study outcome, we extended the trial an additional 6 months to evaluate the robustness of the findings. Herein, we report on the 12-month findings. At baseline, treatment-naïve patients with choroidal neovascularization secondary to AMD were genotyped for CFH haplotypes, SNP rs2230199 (C3), SNP rs10490824 (ARMS2), and the mtDNA A4917G marker. The primary study outcome was a gain of ≥15 letters in patients with risk alleles or haplotypes for AMD. Secondary outcome measures sought to identify associations between genetic dispositions and change in visual acuity (VA) or central macular thickness. Intravitreal ranibizumab at a concentration of 0.5 mg/0.05 mL was used to treat patients. All patients received 3 monthly injections followed by a flexible pro re nata regimen. Of the 70 patients included in the 6-month analysis, 60 participated in the extended study. The 10 Received: February 7, 2017 Accepted after revision: August 31, 2017 Published online: January 26, 2018