Multifocal pupillography identifies Ranibizumab-induced changes in retinal function for exudative age-related macular degeneration

PURPOSE. To investigate the efficacy of multifocal pupillographic objective perimetry (mfPOP) to quantify the effects of intravitreal ranibizumab injection for choroidal neovascularization (CNV) secondary to exudative age-related macular degeneration (AMD). METHODS. mfPOP visual fields from 20 patients with unilateral exudative AMD treated with intravitreal ranibizumab were measured before and after 3 months of treatment and were compared with that in 30 normal subjects. Two stimulus types consisting of ensembles of 24 or 44 independent stimuli per eye had a mean presentation interval at each region of 1 second. Pupil responses were recorded with video cameras under infrared illumination. Multiple linear models were fitted to contraction amplitudes and delay to peak responses, to determine the independent effects of exudative AMD before and after ranibizumab therapy. RESULTS. After 3 months of treatment, mean additional response delays compared to normal subjects for the 24-region stimulus improved significantly (P < 5 × 10 -9) from a mean of 18.82 ± 3.0 ms at baseline to 7.45 ± 3.15 ms. The mean effect of exudative AMD at baseline decreased constriction amplitude by -1.11 ± 0.24 dB (P < 0.00001) with little improvement after ranibizumab therapy. Small pretreatment elevations of extrafoveal sensitivity correlated with improvements in central retinal thickness (CRT) after treatment (P < 0.0005). CONCLUSIONS. Improvements in mfPOP contraction amplitudes and time to peak responses were measured in eyes treated with intravitreal ranibizumab; however, response delays appeared to be the most indicative of functional improvement. Confirmation of hypersensitivity in the extrafoveal field in a larger group may support this finding as a prognostic marker for good treatment outcomes

Blue multifocal pupillographic objective perimetry in glaucoma

PURPOSE. This study investigated multifocal pupillographic objective perimetry (mfPOP) stimuli that target the intrinsic photosensitivity of melanopsin retinal ganglion cells. The diagnostic potential for glaucoma is compared between stimuli biased toward either cone input to these cells or their melanopsin response. METHODS. Nineteen glaucoma patients and 24 normal subjects were tested using mfPOP stimulus protocols with either 33-ms yellow or 750-ms blue stimuli. Subjects’ color discrimination was assessed using the Farnsworth 100-hue test. Pupillary responses were measured, and mixed-effects regression was used to quantify results. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis. RESULTS. The mean reduction in moderate to severe glaucoma pupil responses using blue mfPOP stimuli was larger but more variable than that of the shorter yellow stimuli (blue:1.32 dB [t(40) ¼ 2.29; P ¼ 0.027]; yellow: 0.93 dB [t(40) ¼ 3.13; P ¼ 0.003]). Color discrimination decreased significantly with age and glaucoma, with type III blue-yellow anomalies dominating. ROC analysis revealed similar diagnostic accuracies (AUC for eyes classified as moderate to severe; blue: 81.7%, yellow: 83.7). Slightly higher sensitivity and specificity were obtained using blue stimuli in mild disease (AUCs blue: 71.1, cf. yellow: 67.7), although this difference was not significant. CONCLUSIONS. In moderate to severe glaucoma, diagnostic accuracy of yellow and blue was similar, but blue stimuli showed limited ability to resolve scotomas. Blue mfPOP stimuli, however, may have advantages over yellow in detecting early glaucoma

Topical chloramphenicol usage in Australia pre- and post-rescheduling as a non-prescription medication – Supplementary Material

Chloramphenicol is the most commonly prescribed topical antibiotic in Australia. For the first time, we quantify the prescribing and dispensing rates for topical chloramphenicol before and after the rescheduling of chloramphenicol as a Schedule 3 (Pharmacist Only Medication, not requiring a written prescription, for ophthalmic use only) medication in Australia for the treatment of bacterial conjunctivitis (BC). We take into consideration other ophthalmic and non-ophthalmic uses for topical chloramphenicol in order to make valid comparisons between the pre- and post-rescheduling dispensing rates for BC alone. Per capita dispensing rates for topical chloramphenicol for BC before and after rescheduling appear to be in excess of any estimated incidence of BC, with a significant rise in the number of units of chloramphenicol dispensed per capita for BC subsequent to rescheduling. Topical chloramphenicol prescribing for BC both pre- and post-rescheduling suggests that treatment guidelines and referral paradigms for anterior ocular pathology in Australia should be reviewed

Comparing multifocal pupillographic objective perimetry (mfPOP) and multifocal visual evoked potentials (mfVEP) in retinal diseases

Multifocal pupillographic objective perimetry (mfPOP) shows regions of slight hypersensitivity away from retinal regions damaged by diabetes or age-related macular degeneration (AMD). This study examines if such results also appear in multifocal visual evoked potentials (mfVEPs) recorded on the same day in the same patients. The pupil control system receives input from the extra-striate cortex, so we also examined evidence for such input. We recruited subjects with early type 2 diabetes (T2D) with no retinopathy, and patients with unilateral exudative AMD. Population average responses of the diabetes patients, and the normal fellow eyes of AMD patients, showed multiple regions of significant hypersensitivity (p < 0.05) on both mfPOP and mfVEPs. For mfVEPs the occipital electrodes showed fewer hypersensitive regions than the surrounding electrodes. More advanced AMD showed regions of suppression becoming centrally concentrated in the exudative AMD areas. Thus, mfVEP electrodes biased towards extra-striate cortical responses (surround electrodes) appeared to show similar hypersensitive visual field locations to mfPOP in early stage diabetic and AMD damage. Our findings suggest that hypersensitive regions may be a potential biomarker for future development of AMD or non-proliferative diabetic retinopathy, and may be more informative than visual acuity which remains largely undisturbed during early disease

Rapid Objective Testing of Visual Function Matched to the ETDRS Grid and Its Diagnostic Power in Age-Related Macular Degeneration

Purpose: To study the power of an 80-second multifocal pupillographic objective perimetry (mfPOP) test tailored to the ETDRS grid to diagnose age-related macular degeneration (AMD) by Age-Related Eye Disease Study (AREDS) severity grade. Design: Evaluation of a diagnostic technology. Methods: We compared diagnostic power of acuity, ETDRS grid retinal thickness data, new 80-second M18 mfPOP test, and two wider-field 6-minute mfPOP tests (Macular-P131, Widefield-P129). The M18 stimuli match the size and shape of bifurcated ETDRS grid regions, allowing easy structure–function comparisons. M18, P129, and P131 stimuli test both eyes concurrently. We recruited 34 patients with early-stage AMD with a mean ± standard deviation (SD) age of 72.6 ± 7.06 years. The M18 and P129 plus P131 stimuli had 26 and 51 control participants, respectively with mean ± SD ages of 73.1 ± 8.17 years and 72.1 ± 5.83 years, respectively. Multifocal pupillographic objective perimetry testing used the Food and Drug Administration-cleared Objective FIELD Analyzer (OFA; Konan Medical USA). Main Outcome Measures: Percentage area under the receiver operator characteristic curve (AUC) and Hedge's g effect size. Results: Acuity and OCT ETDRS grid thickness and volume produced reasonable diagnostic power (percentage AUC) for AREDS grade 4 eyes at 83.9 ± 9.98% and 90.2 ± 6.32% (mean ± standard error), respectively, but not for eyes with less severe disease. By contrast, M18 stimuli produced percentage AUCs from 72.8 ± 6.65% (AREDS grade 2) to 92.9 ± 3.93% (AREDS grade 4), and 82.9 ± 3.71% for all eyes. Hedge's g effect sizes ranged from 0.84 to 2.32 (large to huge). Percentage AUC for P131 stimuli performed similarly and for P129 performed somewhat less well. Conclusions: The rapid and objective M18 test provided diagnostic power comparable with that of wider-field 6-minute mfPOP tests. Unlike acuity or OCT ETDRS grid data, OFA tests produced reasonable diagnostic power in AREDS grade 1 to 3 eyes.</p

Assessing the accuracy of a large observational registry of neovascular age-related macular degeneration

PURPOSE To evaluate the accuracy of an observational database that tracks real-world treatment outcomes for neovascular age-related macular degeneration. METHODS We audited 245 randomly sampled eyes from 189 patients with 3,356 visits from 11 doctors in the Fight Retinal Blindness! DATABASE Sex, birth year, previous treatments received, treatment, and visual acuity were validated against the clinical notes. Error rates, the proportion of missed visits (the number of visits present in the patient record but not entered into Fight Retinal Blindness!), the level of agreement using Cohen's kappa (κ) and intraclass correlation coefficients, and positive and negative predictive values were calculated. A visual acuity error was defined as an absolute difference of ≥5 letters. RESULTS The overall error rate was 3.5% (95% confidence interval: 3.1-3.9). The error rate for visual acuity was 5.1% (95% confidence interval: 4.2-5.9) and <5% for the remaining fields. The level of agreement for each field ranged from good to excellent (κ or intraclass correlation ≥ 0.75). The positive predictive value and negative predictive value for visits were 99% and 89%, respectively. The proportion of missed visits was 10.2%. CONCLUSION Accuracy of the Fight Retinal Blindness! database was good (>95%). The rate of missed visits was high, possibly due to the high burden of retrospective data entry or patients switching practitioners during treatment

Pattern and Presentation of Vitreo-Retinal Diseases: An Analysis of Retrospective Data at a Tertiary Eye Care Center in Nepal

Purpose: We examined patients presenting in a tertiary eye hospital in Nepal, focusing on information relevant to screening and management programs for vitreo-retinal (VR) disease. Design: Retrospective, cross-sectional study. Methods: We reviewed all patients presenting for the first time to the VR-clinic over 1 year. We quantified patient demography, symptoms and duration, systemic diseases, ophthalmological examinations, diagnostic investigations, and final diagnoses. Results: Of the 1905 cases, 1148 were male (60.3%). The 25th percentile of ages was 29 and 38 years for male and female, respectively; thus, female presented later (P < 0.0001). Hypertension was the commonest systemic disease (40.8%), followed by diabetes (32.5%). Age-related macular degeneration (AMD) and diabetic retinopathy (DR) affected 447 eyes (11.8%) and 416 eyes (10.9%), respectively. Male and female AMD and DR patients did not differ in age or disease duration. Similarly, age or disease duration for DR did not correlate with severity. Asymmetry of disease severity between eyes with AMD and DR was largest in patients with 1 normal eye. Presenting acuity was asymmetric between eyes (P < 0.0001) with people more often reporting once their right eyes had acuity of 6/18 or worse. Conclusions: The screening of blood pressure and glucose levels combined with fundus photography could prevent many from progressing to life-changing visual impairment and blindness. Later reporting by females began at childbearing age; therefore, education and ocular screening could be usefully coupled in reproductive health programs. Clubbing VR disease screening with other established health programs like diabetes control program, hypertension clinics, school health program, and so on, would provide economical and sustainable approach

Comparing multifocal pupillographic objective perimetry (mfPOP) and multifocal visual evoked potentials (mfVEP) in retinal diseases

Multifocal pupillographic objective perimetry (mfPOP) shows regions of slight hypersensitivity away from retinal regions damaged by diabetes or age-related macular degeneration (AMD). This study examines if such results also appear in multifocal visual evoked potentials (mfVEPs) recorded on the same day in the same patients. The pupil control system receives input from the extra-striate cortex, so we also examined evidence for such input. We recruited subjects with early type 2 diabetes (T2D) with no retinopathy, and patients with unilateral exudative AMD. Population average responses of the diabetes patients, and the normal fellow eyes of AMD patients, showed multiple regions of significant hypersensitivity (p < 0.05) on both mfPOP and mfVEPs. For mfVEPs the occipital electrodes showed fewer hypersensitive regions than the surrounding electrodes. More advanced AMD showed regions of suppression becoming centrally concentrated in the exudative AMD areas. Thus, mfVEP electrodes biased towards extra-striate cortical responses (surround electrodes) appeared to show similar hypersensitive visual field locations to mfPOP in early stage diabetic and AMD damage. Our findings suggest that hypersensitive regions may be a potential biomarker for future development of AMD or non-proliferative diabetic retinopathy, and may be more informative than visual acuity which remains largely undisturbed during early diseas

Genome-wide association studies for diabetic macular edema and proliferative diabetic retinopathy

Background: Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are sight threatening complications of diabetes mellitus and leading causes of adult onset blindness worldwide. Genetic risk factors for diabetic retinopathy (DR) have been described previously, but have been difficult to replicate between studies, which have often used composite phenotypes and been conducted in different populations. This study aims to identify genetic risk factors for DME and PDR as separate complications in Australians of European descent with type 2 diabetes. Methods: Caucasian Australians with type 2 diabetes were evaluated in a genome wide association study (GWAS) to compare 270 DME cases and 176 PDR cases with 435 non retinopathy controls. All participants were genotyped by SNP array and after data cleaning, cases were compared to controls using logistic regression adjusting for relevant covariates. Results: The top ranked SNP for DME was rs1990145 (p = 4.10 x 10(-6), OR = 2.02 95%CI [1.50, 2.72]) on chromosome 2. The top-ranked SNP for PDR was rs918519 (p = 3.87 x 10(-6), OR = 0.35 95%CI [0.22, 0.54]) on chromosome 5. A trend towards association was also detected at two SNPs reported in the only other reported GWAS of DR in Caucasians; rs12267418 near MALRD1 (p = 0.008) in the DME cohort and rs16999051 in the diabetes gene PCSK.2 (p = 0.007) in the PDR cohort. Conclusion: This study has identified loci of interest for DME and PDR, two common ocular complications of diabetes. These findings require replication in other Caucasian cohorts with type 2 diabetes and larger cohorts will be required to identify genetic loci with statistical confidence. There is considerable overlap in the patient cohorts with each retinopathy subtype, complicating the search for genes that contribute to PDR and DME biology