RetINal Toxicity And HydroxyChloroquine Therapy (INTACT): protocol for a prospective population-based cohort study.

PURPOSE: Hydroxychloroquine (HCQ) is an important medication for patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other rheumatic diseases. Although it is well-tolerated and cost-effective, the risk of HCQ retinal toxicity is of increasing concern. The aim of this study is to re-examine the HCQ retinal toxicity incidence rate, risk factors and clinical course after discontinuation. METHODS: We designed a prospective population-based cohort study in adult patients with SLE or RA, currently receiving HCQ for five or more years, who are residents of British Columbia (BC), Canada. Based on administrative data, we identified 5508 eligible participants (1346 SLE and 4162 RA). They will participate in annual or biannual retinal screening over 5 years in alignment with the recently revised American Academy of Ophthalmology guidelines. To standardise procedures for retinal screening, imaging, diagnostic criteria, severity staging and data transfer, a consensus meeting was convened in December 2019 with participation of BC retinal specialists and the research team. Agreement was attained on: use of spectral domain-optical coherence tomography as the primary objective screening modality; classification of images into categories of normal, equivocal or abnormal; and transferring the equivocal and abnormal images plus corresponding subjective test results via cloud-based server from each clinic to a reading centre. Confirmation of HCQ retinal toxicity diagnoses and severity staging will be performed by three independent and masked reviewers. The incidence of HCQ retinal toxicity will be calculated, accounting for the competing risk of death. Hazard ratios for each risk factor will be calculated for the risk of HCQ retinopathy, after adjusting for confounders. We will also estimate the risk of HCQ retinal toxicity progression over 5 years. ETHICS AND DISSEMINATION: This study has received approval from the University of British Columbia Clinical Research Ethics Board (H20-00736) and the Vancouver Coastal Health Research Institute.

VOLUMETRIC ASSESSMENT OF THE RESPONSIVENESS OF PIGMENT EPITHELIAL DETACHMENTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TO INTRAVITREAL BEVACIZUMAB.

PURPOSE: To determine baseline factors that can predict the response of pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration to treatment with intravitreal bevacizumab (IVB). METHODS: Patients with newly diagnosed neovascular age-related macular degeneration and PED who were treated exclusively with IVB were included. Response to treatment was defined by change in PED volume (determined using spectral-domain optical coherence tomography). PEDs were classified as either predominantly serous or fibrovascular. Multivariable regression and receiver operating characteristic analyses were performed. RESULTS: A total of 48 eyes were identified (mean follow-up time 73 weeks). Overall, the response to the first IVB treatment was predictive of the response to treatment at the final visit (P = 0.015). Serous PEDs had a greater decrease in volume at the final visit (P = 0.008). With respect to both PED types, a decrease in PED volume of 21% after the first IVB treatment was predictive of an overall decrease in volume of 30% at the final visit (sensitivity 83%, specificity 76%). CONCLUSION: In neovascular age-related macular degeneration, serous PEDs respond more favorably to IVB than fibrovascular PEDs. Overall, for both types of PED, the response to the first treatment is predictive of the final response to treatment. Taken together, the results would suggest that if there is less than 21% reduction in PED volume after the first IVB treatment, and/or the PED is predominantly fibrovascular, then switching to another antivascular endothelial growth factor agent should be considered.

Optical coherence tomography-based measurement of drusen load predicts development of advanced age-related macular degeneration.

PURPOSE: To determine whether baseline drusen load, as measured using spectral-domain optical coherence tomography (SD OCT), is a useful predictor of development of advanced age-related macular degeneration (AMD). DESIGN: Retrospective cohort study. METHODS: setting: Academic clinical practice. study population: All patients with non-neovascular AMD and no retinal pigment epithelial (RPE) atrophy at baseline who were seen between 2007 and 2012 in a single academic retina practice. A minimum of 1 year of follow-up was required. observation: Drusen load (area and volume) was assessed using automated SD OCT software algorithms. main outcome measure: RPE atrophy area, assessed using an automated SD OCT software algorithm, and the development of neovascular AMD. RESULTS: Eighty-three patients met the inclusion criteria with a mean age of 80 years and a mean follow-up time of 2.8 years. Repeated-measures analysis of variance showed an association between drusen area (P = .005) and drusen volume (P = .001) and the development of RPE atrophy. We also found an association between drusen area (P = .001) and drusen volume (P = .001) and the development of neovascular AMD. CONCLUSIONS: Drusen load, as measured using SD OCT, is associated with the development of RPE atrophy and neovascular AMD. SD OCT assessments of drusen load are simple and practical measurements that may be useful in stratifying the risk of developing advanced AMD. These measurements have potential applications in both routine clinical care and clinical trials.

Exacerbation of choroidal and retinal pigment epithelial atrophy after anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration.

PURPOSE: To study the progression of retinal pigment epithelium (RPE) and choroidal atrophy in patients with neovascular age-related macular degeneration (AMD) and to assess for a possible association with the number and type of anti-vascular endothelial growth factor treatments. METHODS: Patients with neovascular AMD and a minimum of 1-year follow-up were reviewed. Fellow eyes with nonneovascular AMD were used as control eyes. Retinal pigment epithelial atrophy area and choroidal thickness were determined using spectral-domain optical coherence tomography. Multivariable regression models were used for statistical analyses. RESULTS: A total of 415 eyes were included in the study, with a mean follow-up of 2.2 years. Eyes with neovascular AMD had greater progression of RPE atrophy and choroidal atrophy compared with those with nonneovascular AMD (P < 0.001). Progression of RPE atrophy and choroidal atrophy was independently associated with the total number of injections of bevacizumab and ranibizumab (all P values ≤ 0.001). In the subgroup of 84 eyes with neovascular AMD and without RPE atrophy at baseline, only bevacizumab was associated with the progression of RPE atrophy (P = 0.003). This study likely lacked statistical power to detect an association with ranibizumab in this subgroup. CONCLUSION: Retinal pigment epithelial atrophy and choroidal atrophy in neovascular AMD seem to be exacerbated by anti-vascular endothelial growth factor treatment. Possible differences between bevacizumab and ranibizumab require further investigation.

Unilateral hypoplasia of the trigeminal ganglion.

CASE REPORT: We report a case of unilateral anaesthesia of the V1 (ophthalmic) division of the trigeminal cranial nerve presenting with persistent corneal erosions and ulceration secondary to trigeminal ganglion hypoplasia. The patient had a lifelong history of unexplained left-sided ophthalmic symptoms for which numerous diagnoses were provided. Cranial nerve testing demonstrated partial trigeminal dysfunction on the left side. Further investigation eliminated viral etiologies, and subsequent magnetic resonance imaging determined that the patient had a hypo-plastic left trigeminal ganglion. COMMENTS: We present the case to alert clinicians to the possibility of this rare condition.

Negative predictive value of a vision screening program aimed at children aged 3 to 4 years old.

PURPOSE: Nova Scotia has a vision screening program which assesses children aged 4[1\2] to 5[1\2] years. However, its use in younger children proved impossible. This study will examine a modified screening protocol for the younger children (3 to 4 years old) and determine its negative predictive value and minimum age for reliable application. MATERIALS AND METHODS: Public health nurses administered the study protocol to 3- to 4-year-old children. One hundred seventy-eight children were screened over two summers. Medical and family history, external inspection, as well as measures of visual acuity with the Lea Hyvarinen symbols chart and stereoacuity with Frisby plates were recorded. Results were compared with a gold standard examination that included full orthoptic and ophthalmologic evaluations. One hundred forty-one (79%) children underwent the gold standard examination. Agreement between screening and gold standard examinations was studied. RESULTS: Data showed increased concordance between screening and gold standard examination results with increasing age up to 41 months. Negative predictive value (NPV) and specificity also improved when data were separated by this age. In children <41 months old, the screening test NPV was 90%, specificity, 68%, and sensitivity, 75%. In comparison, children >/=41 months old had screening test NPV of 96%, specificity, 95%, and sensitivity, 50%. Specificity was higher in the older age group ( P < 0.001). Sensitivity was lower ( P = 0.004). CONCLUSION: This study's vision screening protocol appears better suited for children 41 months and older. They had better pass/fail reproducibility than children <41 months. The test's simplicity allows easy use by non-eye-care professionals. It could potentially lower the reliable screening age of children by 13 months, from 54 months of age (4[1\2] years old) to 41 months. This screening may miss some refractive errors and microtropia/monofixation syndrome, despite normal visual acuity, stereoacuity, and external inspection.