Visual Field Tests: A Narrative Review of Different Perimetric Methods.

Visual field (VF) testing dates back to fifth century B.C. It plays a pivotal role in the diagnosis, management, and prognosis of retinal and neurological diseases. This review summarizes each of the different VF tests and perimetric methods, including the advantages and disadvantages and adherence to the desired standard diagnostic criteria. The review targets beginners and eye care professionals and includes history and evolution, qualitative and quantitative tests, and subjective and objective perimetric methods. VF testing methods have evolved in terms of technique, precision, user-friendliness, and accuracy. Consequently, some earlier perimetric techniques, often still effective, are not used or have been forgotten. Newer technologies may not always be advantageous because of higher costs, and they may not achieve the desired sensitivity and specificity. VF testing is most often used in glaucoma and neurological diseases, but new objective methods that also measure response latencies are emerging for the management of retinal diseases. Given the varied perimetric methods available, clinicians are advised to select appropriate methods to suit their needs and target disease and to decide on applying simple vs. complex tests or between using subjective and objective methods. Newer, rapid, non-contact, objective methods may provide improved patient satisfaction and allow for the testing of children and the infirm.

The structure-function relationship between multifocal pupil perimetry and retinal nerve fibre layer in glaucoma.

BACKGROUND: Multifocal pupillographic objective perimetry (mfPOP) is a novel method for assessing functional change in diseases like glaucoma. Previous research has suggested that, in contrast to the pretectally-mediated melanopsin response of intrinsically photosensitive retinal ganglion cells, mfPOP responses to transient onset stimuli involve the extrastriate cortex, and thus the main visual pathway. We therefore investigate the correlation between peripapillary retinal nerve fibre layer (pRNFL) thickness and glaucomatous visual field changes detected using mfPOP. Parallel analyses are undertaken using white on white standard automated perimetry (SAP) for comparison. METHODS: Twenty-five glaucoma patients and 24 normal subjects were tested using SAP, 3 mfPOP variants, and optical coherence tomography (OCT). Arcuate clusters of the SAP and mfPOP deviations were weighted according to their contribution to published arcuate divisions of the retinal nerve fibre layer. Structure-function correlation coefficients (r) were computed between pRNFL clock-hour sector thickness measurements, and the local visual field sensitivities from both SAP and mfPOP. RESULTS: The strongest correlation was observed in the superior-superotemporal disc sector in patients with worst eye SAP MD < -12 dB: r = 0.93 for the mfPOP LumBal test (p < 0.001). Correlations across all disc-sectors were strongest in these same patients in both SAP and mfPOP: SAP r = 0.54, mfPOP LumBal r = 0.55 (p < 0.001). In patients with SAP MD ≥ -6 dB in both eyes, SAP correlations across all sectors were higher than mfPOP; mfPOP correlations however, were higher than SAP in more advanced disease, and in normal subjects. CONCLUSIONS: For both methods the largest correlations with pRNFL thickness corresponded to the inferior nasal field of more severely damaged eyes. Head-to-head comparison of mfPOP and SAP showed similar structure-function relationships. This agrees with our recent reports that mfPOP primarily stimulates the cortical drive to the pupils.

Comparing 2-dimensional macular pigment optical density with objective and subjective perimetry and visual acuity in age-related macular degeneration.

PURPOSE: To compare diagnostic power for different severities of age-related macular degeneration (AMD) of two-dimensional macular pigment optical densities (2D-MPOD) and spatially matched objective perimetry, with standard perimetry and best-corrected visual acuity (BCVA). METHODS: The ObjectiveField Analyser (OFA) provided objective perimetry, and a Heidelberg Spectralis optical coherence tomography (OCT) measured 2D-MPOD in AMD patients, both completed twice over 0.99 ± 0.16 years. From each 2D-MPOD image, we extracted 20 regions/macula, matched to the 20 OFA stimuli/macula. For each region, we calculated 7 measures from the 2D-MPOD pixel values and correlated those with OFA sensitivities and delays. We quantified 2D-MPOD changes, the ability of 2D-MPOD and OFA to discriminate AMD stages, and the discriminatory power of Matrix perimetry and BCVA using percentage area under receiver operator characteristic plots (%AUROC). RESULTS: In 58 eyes of 29 subjects (71.6 ± 6.3 years, 22 females), we found significant correlations between 2D-MPOD and OFA sensitivities for Age-Related Eye Disease Studies (AREDS)-3 and AREDS-4 severities. Delays showed significant correlations with AREDS-2. For AREDS-4, correlations extended across all eccentricities. Regression associated with the Bland-Altman plots showed significant changes in 2D-MPOD over the study period, especially variability measures. MPOD per-region medians discriminated AREDS-1 from AREDS-3 eyes at a %AUROC of 80.0 ± 6.3%, outperforming OFA, Matrix perimetry, and BCVA. CONCLUSIONS: MPOD changes correlated with central functional changes and significant correlations extended peripherally in later-stage AMD. Good diagnostic power for earlier-stage AMD and significant change over the study suggest that 2D-MPOD and OFA may provide effective biomarkers.

Early diabetic eye damage: Comparing detection methods using diagnostic power.

It is now clear that retinal neuropathy precedes classical microvascular retinopathy in diabetes. Therefore, tests that underpin useful new endpoints must provide high diagnostic power well before the onset of moderate diabetic retinopathy. Hence, we compare detection methods of early diabetic eye damage. We reviewed data from a range of functional and structural studies of early diabetic eye disease and computed standardized effect size as a measure of diagnostic power, allowing the studies to be compared quantitatively. We then derived minimum performance criteria for tests to provide useful clinical endpoints. This included the criteria that tests should be rapid and easy so that children with type 1 diabetes can be followed into adulthood with the same tests. We also defined attributes that lend test data to further improve performance using Machine/Deep Learning. Data from a new form of objective perimetry suggested that the criteria are achievable.

A Review of the Categorizations of Mild, Moderate, and Severe Bacterial Keratitis Ulcers and Day-1 Treatment Regimen When Using the Topical Fluoroquinolones 0.3% Ciprofloxacin and 0.3% Ofloxacin.

Background: There are published suggestions that bacterial keratitis (BK) can be classified as mild, moderate, or severe and that the day-1 antibiotic drop regimen may differ for each category using the topical second-generation fluoroquinolones 0.3% ciprofloxacin and 0.3% ofloxacin (2FQ). The classification criteria are not consistently defined and the suggested regimens are often unreferenced and so here, the evidence base for applying such regimens in clinical practice is examined. Objective: To examine the evidence base regarding the categorization criteria used for BK and determine whether any evidence exists to support suggestions that different day-1 treatment regimen using the 2FQ may be applied based on any assigned categorization. Methods: The literature on BK treatment was reviewed, as were the clinical studies involving the commercially available 2FQ. All statements pertaining to classification and treatment paradigms involving BK were then collated and reviewed, as were the methodologies employed in the 2FQ clinical studies. Results: There have been no clinical trials using the 2FQ, or indeed any other topical antibiotics, which have used different day-1 drop regimen depending on the size, depth, and location of the ulcer or for ulcers classified as mild, moderate, or severe. Thus, there is no evidence to support the suggestion that a lower number of drops on day 1 is as effective as a higher number on categorized BK ulcers. Conclusions: No standardized method of categorizing BK was found, and there is no evidence to support the contention that mild, moderate, or smaller BK ulcers should be treated any differently to larger or severe ulcers on day 1. The manufacturers of 2FQ do not supply different treatment regimens for different ulcer sizes and severity categories. When using the 2FQ, all BK ulcers should be treated equally in line with the manufacturers' recommended day-1 treatment regimen.

Report From the 2022 Mary Tyler Moore Vision Initiative Diabetic Retinal Disease Clinical Endpoints Workshop.

The Mary Tyler Moore Vision Initiative Diabetic Retinal Disease (DRD) Clinical Endpoints Workshop was held on October 22, 2022 to accelerate progress toward establishment of useful clinical and research endpoints and development of new therapeutics that have important relevance across the full spectrum of DRD pathology. More than 90 patient representatives, clinicians, scientists, funding and regulatory agencies, diagnostic, therapeutic and biotech industry representatives discussed the needs for new diagnostic and therapeutic approaches to prevent and restore retinal neurovascular unit integrity. Phase I of the MTM Vision Initiative plans, notably updating the DRD staging system and severity scale, establishing a human ocular biorepository and resource, and clinical endpoints and biomarker development and validation, was emphasized.

Profile of Patients Treated with Intravitreal Anti-Vascular Endothelial Growth Factor Injections in Bhutan.

Purpose: Ocular vascular diseases are common causes of visual impairment and blindness, for which anti-vascular endothelial growth factor (anti-VEGF) is the first-line therapy. Current study describes the profile of patients receiving intravitreal anti-VEGF injections (IVI), and gender variation in Bhutan. The study was designed to inform national health policy. Study Design: Retrospective cross-sectional study. Methods: We reviewed the surgical registers of the vitreoretinal (VR) units across Bhutan over three years. Patient demography, clinical findings, diagnostic tests performed, and diagnoses or indications for IVI were logged. A descriptive analysis was performed. Results: Despite limited availability of anti-VEGF, a total of 381 patients received IVI in operating theatres as mandated by the national guidelines. The majority of patients were males (230, 60.4%, p = 0.004). The mean age was 65.2 ± 13.5 years (range 13 years to 90 years), and a median of 69 years. The majority of the treated eyes (117, 30.7%) had BCVA <3/60 to light perception (PL), and another 51 eyes (13.4%) had < 6/60 to 3/60. The most common indication for IVI was neovascular age-related macular degeneration (nAMD) (168 cases, 42.2%), followed by retinal vein occlusion (RVO) (132 cases, 34.6%), diabetic macular oedema (DMO) and retinopathy (DR) (50 cases, 13.1%), and myopic choroidal neovascular membrane (11 cases, 0.03%). Conclusion: Limited human resources for managing VR diseases in Bhutan are compounded by economic and geographic challenges. With increasing VR diseases such as nAMD and myopia and complications of systemic diseases such as DR, DMO and RVO, there is a need to improve VR services. Currently, anti-VEGF is procured only for a pooled patients requiring IVI, and patients are lost due to longer waiting periods. Bhutan needs to assess if females are reporting less or are not receiving treatment due to cultural barriers and social stigma.

Objective perimetry identifies regional functional progression and recovery in mild Diabetic Macular Oedema.

PURPOSE: Retinal function beyond foveal vision is not routinely examined in the clinical screening and management of diabetic retinopathy although growing evidence suggests it may precede structural changes. In this study we compare optical coherence tomography (OCT) based macular structure with function measured objectively with the ObjectiveFIELD Analyzer (OFA), and with Matrix perimetry. We did that longitudinally in Type 2 diabetes (T2D) patients with mild Diabetic Macular Oedema (DMO) with good vision and a similar number of T2D patients without DMO, to evaluate changes in retinal function more peripherally over the natural course of retinopathy. METHODS: Both eyes of 16 T2D patients (65.0 ± 10.1, 10 females), 10 with baseline DMO, were followed for up longitudinally for 27 months providing 94 data sets. Vasculopathy was assessed by fundus photography. Retinopathy was graded using to Early Treatment of Diabetic Retinopathy Study (ETDRS) guidelines. Posterior-pole OCT quantified a 64-region/eye thickness grid. Retinal function was measured with 10-2 Matrix perimetry, and the FDA-cleared OFA. Two multifocal pupillographic objective perimetry (mfPOP) variants presented 44 stimuli/eye within either the central 30° or 60° of the visual field, providing sensitivities and delays for each test-region. OCT, Matrix and 30° OFA data were mapped to a common 44 region/eye grid allowing change over time to be compared at the same retinal regions. RESULTS: In eyes that presented with DMO at baseline, mean retinal thickness reduced from 237 ± 25 µm to 234.2 ± 26.7 µm, while the initially non-DMO eyes significantly increased their mean thickness from 250.7 ± 24.4 µm to 255.7 ± 20.6 µm (both p<0.05). Eyes that reduced in retinal thickness over time recovered to more normal OFA sensitivities and delays (all p<0.021). Matrix perimetry quantified fewer regions that changed significantly over the 27 months, mostly presenting in the central 8 degrees. CONCLUSIONS: Changes in retinal function measured by OFA possibly offer greater power to monitor DMO over time than Matrix perimetry data.

Prevalence and severity of diabetic retinopathy at first presentation to vitreoretinal services in Bhutan: a 3-year national study.

PURPOSE: To determine the prevalence and severity of diabetic retinopathy (DR) at first presentation among diabetic patients attending national vitreoretinal (VR) services in Bhutan STUDY DESIGN: Retrospective cross-sectional study METHODS: We included all diabetic patients in Bhutan who presented for retinal evaluation for the first time over a 3-year period (2013-2016). Data including demography, clinical details, diagnostic tests, and clinical staging of DR were analyzed. RESULTS: A total of 843 diabetic patients, aged 57.2 ± 12.0 (range 18-86) years, were enrolled. The majority were male (452, 53.6%; cumulative frequency [cf] 391, 46.4%; P = .14) and from urban settings (570, 67.6%; cf 273; 32.4%) and did not have modern schooling (555, 65.8%). Hypertension was the most common systemic comorbidity (501, 59.4%). The prevalence of DR was 42.7%, with mild nonproliferative DR (NPDR) being the most common type (187, 51.9%), followed by moderate NPDR (88, 24.4%) and proliferative DR (45, 12.5%). In addition, 120 patients had clinically significant macular edema (CSME), with a prevalence of 14.2%. Best-corrected visual acuity (BCVA) of 6/60 or worse occurred in 231 eyes (13.7%), and 41 patients (4.86%) had BCVA of 6/60 or worse bilaterally due to DR/CSME. A logistic regression model indicated that the major determinant of DR was the duration of diabetes, the odds rising by 1.27× with each year of disease (P < .0001). CONCLUSION: The prevalence of DR, including CSME, was high. Although a national DR screening program is established in Bhutan, there is a need to accelerate health education, community screening, and referral systems to reduce the prevalence of DR and CSME.

The experience of visual art for people living with mild-to-moderate vision loss.

BACKGROUND: Visual art can enhance wellbeing and quality-of-life; however, the experience of visual art for people with mild-to-moderate vision loss has not been examined. METHODS: Eight participants (6 females, 2 males; Mean age = 81 years, SD = 7.9, range 70-91 years; 4 with mild vision loss and 4 with moderate vision loss based on binocular visual acuity) completed a mixed-methods study comprising: a semi-structured interview on visual art experience; an eye examination; and questionnaires about visual functioning and quality-of-life. RESULTS: Various themes were identified: visual perception of art (e.g. altered colours, visual distortions, etc.), viewing conditions, elements of art, personal preference, deriving meaning, appreciation of art, impact of impaired visual perception, and social aspects of art. CONCLUSIONS: The overall experience of art is influenced by how an individual sees, perceives, and makes meaning from art. Even mild vision loss can impair this experience and impact emotional and social wellbeing.

Incidence and Pattern of Neuro-Ophthalmological Disorders Presenting to Vitreoretinal Clinics in Bhutan: A 3-Year National Study.

Purpose: To inform national health policy, we quantified the pattern of neuro-ophthalmological disorders (NODs) presenting to the national vitreoretinal clinics in Bhutan. Study Design: Retrospective cross-sectional study. Methods: We reviewed all new NODs patients over three years. Demographic data, presenting complaints, treatment history, systemic diseases, diagnostic procedures, and diagnoses were quantified. Logistic regression examined the odds of factors linked to more common NODs. Results: Of 226 patients, the majority were males (54.0%), farmers (60.2%), and urbanites (55.8%). Loss of vision was the most common presenting complaint (57.9%), followed by head or orbital trauma (19.5%). The best corrected visual acuity (BCVA) of 216 eyes (47.8%) was ≤6/60. Hypertension was the most common systemic disease (16.4%), followed by diabetes (3.5%), and intracranial space-occupying lesions (3.5%). Neuroimaging (37.6%) was the most common diagnostic test performed, followed by visual field testings (VFTs) (22.9%). With a NOD incidence of 7.8% p.a. (226/2913), optic atrophy (OA) was diagnosed in 134 patients (59.3%). Other common NODs were optic neuritis (15.5%), papilloedema (9.3%), and traumatic optic neuropathy (8.4%). Female gender increased the odds for glaucomatous OA by 2.65× (p = 0.044), and age by 1.09× per year (p < 0.001). Being female increased the odds of optic neuritis by 2.57× (p = 0.03). Conclusion: Over half of the NODs were OA, which could be curable with timely treatment. Improved treatment of glaucoma and non-communicable diseases would reduce the risk of NODs-induced visual loss in Bhutan. The need for improved neuro-ophthalmological assessment and a coordinated multidisciplinary approach to NODs are the highest priorities.

A Literature-Based Review and Analysis of the Pharmacodynamics of the Dose Frequency of Topical 0.3% Ciprofloxacin and 0.3% Ofloxacin in the Day-1 Treatment of Bacterial Keratitis.

Purpose: To determine the appropriate dose frequency for the second-generation fluoroquinolones (2FQs), ciprofloxacin 0.3% and ofloxacin 0.3%, in the day-1 treatment of bacterial keratitis (BK) based on the corneal concentrations achievable and required Minimum Inhibitory Concentration90 (MIC90) of common BK isolates. Methods: Literature-based ocular MIC90 required to treat bacterial isolates of BK patients were determined for each fluoroquinolone. Published corneal concentrations for each 2FQ, and the drop regimens used to reach these concentrations, were then analyzed to determine the relationship between the corneal 2FQ concentration and the amount of drug applied per hour and the total amount applied. Results: Significant relationships were found to exist for corneal concentrations of both ciprofloxacin and ofloxacin and the amount of drug applied per hour (both P = 0.005), and the total amount of drug applied (P = 0.003 and P = 0.0004, respectively). Derived ciprofloxacin drops/hour corneal concentrations agreed well with both a literature-based regimen and the manufacturers' day-1 drop regimen for various MIC90. Derived ofloxacin drops per hour indicated a higher rate than that suggested by the manufacturer. Conclusions: Both a literature-based and the manufacturers' drop regimens for the day-1 treatment of BK using 0.3% ciprofloxacin have a pharmacodynamic basis, which is related to the required MIC90 of commonly encountered isolates in BK. Dose frequency for 0.3% ofloxacin should be in line with the manufacturers' maximum suggested drop regimen. Commonly suggested drop regimens below these recommendations for either FQ may need to be revised in view of these findings.

Rapid, non-contact multifocal visual assessment in multiple sclerosis.

OBJECTIVE: Previous work on temporally sparse multifocal methods suggests that the results are correlated with disability and progression in people with multiple sclerosis (PwMS). Here, we assess the diagnostic power of three cortically mediated sparse multifocal pupillographic objective perimetry (mfPOP) methods that quantified response-delay and light-sensitivity at up to 44 regions of both visual fields concurrently. METHODS: One high-spatial-resolution mfPOP method, P129, and two rapid medium-resolution methods, W12 and W20, were tested on 44 PwMS and controls. W12 and W20 took 82 s to test both visual fields concurrently, providing response delay and sensitivity at each field location, while P129 took 7 min. Diagnostic power was assessed using areas under the receiver operating characteristic (AUROC) curves and effect-size (Hedges' g). Linear models examined significance. Concurrent testing of both eyes permitted assessment of between-eye asymmetries. RESULTS: Per-region response delays and asymmetries achieved AUROCs of 86.6% ± 4.72% (mean ± SE) in relapsing-remitting MS, and 96.5% ± 2.30% in progressive MS. Performance increased with increasing disability scores, with even moderate EDSS 2 to 4.5 PwMS producing AUROCs of 82.1 to 89.8%, Hedge's g values up to 2.06, and p = 4.0e - 13. All tests performed well regardless of any history of optic neuritis. W12 and W20 performed as well or better than P129. CONCLUSION: Overall, the 82-s tests (W12 and W20) performed better than P129. The results suggest that mfPOP assesses a correlate of disease severity rather than a history of inflammation, and that it may be useful in the clinical management of PwMS.

Discriminating early-stage diabetic retinopathy with subjective and objective perimetry.

Introduction: To prevent progression of early-stage diabetic retinopathy, we need functional tests that can distinguish multiple levels of neural damage before classical vasculopathy. To that end, we compared multifocal pupillographic objective perimetry (mfPOP), and two types of subjective automated perimetry (SAP), in persons with type 2 diabetes (PwT2D) with either no retinopathy (noDR) or mild to-moderate non-proliferative retinopathy (mmDR). Methods: Both eyes were assessed by two mfPOP test methods that present stimuli within either the central ±15° (OFA15) or ±30° (OFA30), each producing per-region sensitivities and response delays. The SAP tests were 24-2 Short Wavelength Automated Perimetry and 24-2 Matrix perimetry. Results: Five of eight mfPOP global indices were significantly different between noDR and mmDR eyes, but none of the equivalent measures differed for SAP. Per-region mfPOP identified significant hypersensitivity and longer delays in the peripheral visual field, verifying earlier findings. Diagnostic power for discrimination of noDR vs. mmDR, and normal controls vs. PwT2D, was much higher for mfPOP than SAP. The mfPOP per-region delays provided the best discrimination. The presence of localized rather than global changes in delay ruled out iris neuropathy as a major factor. Discussion: mfPOP response delays may provide new surrogate endpoints for studies of interventions for early-stage diabetic eye damage.

The safety and tolerability of levodopa eye drops for the treatment of ocular disorders: A randomized first-in-human study.

Myopia is the leading cause of low vision worldwide and can lead to significant pathological complications. Therefore, to improve patient outcomes, the field continues to develop novel interventions for this visual disorder. Accordingly, this first-in-human study reports on the safety profile of a novel dopamine-based ophthalmic treatment for myopia, levodopa/carbidopa eye drops. This phase I, first-in-human, monocenter, placebo-controlled, double-blind, paired-eye, multidose, randomized clinical trial was undertaken in healthy adult males aged 18-30 years (mean age 24.9 ± 2.7) at the University of Canberra Eye Clinic, Australia. Participants were randomly assigned to receive either a low (1.4 levodopa:0.34 carbidopa [µmoles/day], n = 14) or standard dose (2.7 levodopa:0.68 carbidopa [µmoles/day], n = 15) of levodopa/carbidopa eye drops in one eye and placebo in the fellow eye once daily for 4 weeks (28 days). Over this 4-week trial, and after a 4-month follow-up visit, levodopa/carbidopa treatment had no significant effect on ocular tolerability and anterior surface integrity, visual function, ocular health, refraction/ocular biometry, and did not induce any non-ocular adverse events. These results indicate that topical levodopa/carbidopa is safe and tolerable to the eye, paving the way for future studies on the efficacy of this novel ophthalmic formulation in the treatment of human myopia. The findings of this study have implications not only for the treatment of myopia, but in a number of other visual disorders (i.e., amblyopia, diabetic retinopathy, and age-related macular degeneration) in which levodopa has been identified as a potential clinical intervention.

Objective perimetry and progression of multiple sclerosis.

Introduction: We re-examined the per-region response amplitudes and delays obtained from multifocal pupillographic objective perimetry (mfPOP) after 10 years in 44 persons living with multiple sclerosis (PwMS), both to examine which parts of the visual field had progressed in terms of response properties and to examine if the baseline data could predict the overall progression of disease. Methods: Expanded Disability Status Scale (EDSS) scores were assessed in 2009 and 2019. Both eyes of each participant were concurrently tested at 44 locations/eye on both occasions. Several measures of clinical progression were examined, using logistic regression to determine the odds of progression. Results: At the second examination the 44 PwMS (31 females) were aged 61.0 ± 12.2 y. Mean EDSS had not changed significantly (3.69 ± 1.23 in 2009, 3.81 ± 2.00 in 2019). mfPOP delay increased progressively from inferior to superior regions of the visual fields while amplitudes demonstrated a temporal to nasal gradient. The mean of the 3 most delayed visual field regions was correlated with progression of MS by 2019 (p = 0.023). Logistic regression indicated a significant association between delay and odds of progression (p = 0.045): an individual with 3 regions at least 1 SD (40 ms) slower than the mean in 2009 had 2.05× (±SE: 1.43× to 2.95×) the odds of progression by 2019. A 1 SD shorter delay was associated with 2.05× lower odds of progression. Amplitude changes were not predictive of progression. Significance: mfPOP may provide a rapid, convenient method of monitoring and predicting MS progression.

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.

Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy.

OBJECTIVE: To evaluate the safety and tolerability of a mineralocorticoid, in a single-dose intravitreal (IVT) injection of 1 mg/0.1 mL and 2 mg/0.1 mL fludrocortisone acetate (FCA) in subjects with geographical atrophy (GA) secondary to age-related macular degeneration. METHODS AND ANALYSIS: This phase 1b study was a two-part dose-escalation prospective study. Part 1 involved a single participant treated with 1 mg/0.1 mL and monitored up to 28 days before being reviewed by a safety review committee. Two subsequent participants were then dosed with the same dose. Part 2 involved a single participant dosed with 2 mg/0.1 mL and monitored up to 28 days when a further five participants were dosed. All participants were followed up for 6 months after baseline.A full ophthalmic assessment was performed at study visits which included GA area, best-corrected visual acuity (BCVA), low-luminance BCVA (LL-BCVA) and intraocular pressure (IOP). Adverse events (AEs) were reported from the first dose of FCA until the end-of-study visit. RESULTS: There were no serious AEs (ocular or systemic) observed with IVT FCA at either 1 mg/0.1 mL or 2 mg/0.1 mL among nine participants. There was no evidence of increased IOP or cataract development.Neither BCVA or LL-BCVA changed significantly in the study-eye over the follow-up period (p=0.28 and 0.38, respectively). Mean GA area increased in the study (0.5 mm2, p=0.003) and fellow-eyes (0.62 mm2, p=0.02) over 6 months. Differences between eyes were not significant (p=0.64), and at the lower end of population norms. CONCLUSION: IVT FCA is clinically safe and well tolerated and did not increase IOP.

Severity of age-related macular degeneration at first presentation in Bhutan: a 3-year national study.

BACKGROUND: Medical services are still developing in Bhutan. There is no published national report on age-related macular degeneration (AMD). We therefore aim to determine the demographic characteristics and severity of AMD at first presentation among Bhutanese patients attending their recently inaugurated vitreoretinal (VR) clinics over a 3-year national survey, and to inform national health policy to develop suitable health program to prevent AMD-related blindness and visual impairment. METHODS: A retrospective cross-sectional consecutive case series study was conducted on all new AMD cases in Bhutan. If a patient presented with asymmetrical AMD, the eye with more severe AMD was considered. If both the eyes had the same severity one eye was chosen randomly. Collection of demographic data and clinical details including diagnostic testing (fundus photography, OCT and fluorescent angiography) and clinical staging were performed. RESULTS: Of 521 new AMD patients aged 71.9 ± 11.3 years, 306/521 (58.7%) were males (p = 0.005). At their first presentation, 234/521 patients (44.9%) already had late-stage AMD. Importantly, 69/234 patients (29.5%), that is half of total neovascular AMD (nAMD) patients, had disciform scars (DS) which were beyond treatment, and 7/234 patients (3.0%) had geographic atrophy (GA). Seven patients had retinal pigment epithelium tear at presentation. Fourteen of nineteen polypoidal choroidal vasculopathy (PCV) patients were younger than 50 years. CONCLUSIONS: Half of nAMD cases presented as DS not amenable to the treatment. Many potentially treatable nAMD patients had already lost central vision and were legally blind. Young people with PCV losing vision early in life with longer morbidity-affected life and socio-economic burden was concerning. GA and DS cases need visual rehabilitation to improve their QoL. Incorporating a screening program for AMD with effective health education, and maintaining a national AMD Registry, would potentially lower AMD-related blindness and visual impairment.

The clinical treatment of bacterial keratitis: A review of drop instillation regimes.

Bacterial keratitis (BK) presentations are often treated using the commercially available second-generation fluoroquinolones ciprofloxacin 0.3% and ofloxacin 0.3% as monotherapy. The guidelines available for instillation regimes are often not supported by data from clinical studies. This review examines the peer-reviewed clinical studies and compared treatment failure rates for ciprofloxacin 0.3% and ofloxacin 0.3% for BK in relation to Day-1 drop-regimes. From the statistical analysis, this review derived evidence-based clinically applicable minimum drop-regimes for the treatment of BK on Day-1. Lower numbers of drops of ciprofloxacin on Day-1 were significantly associated with increased treatment failure rates (p < 0.002). The derived minimum number of drops on Day for ciprofloxacin on Day-1 was 47 drops, and for ofloxacin 24 drops. The mean number of drops used in the clinical studies was significantly lower than the manufacturers' recommended Day-1 regimes for both ciprofloxacin (p = 0.0006) and ofloxacin (p = 0.048). From Day-3 to -6 of treatment the drop rates for ciprofloxacin relative to recommended rates were higher, and for ofloxacin lower (p = 0.014). The findings of this review were then compared with a representative sample of published guidelines and case studies to determine the validity of applying those drop-regimes in clinical practice. Although the manufacturers' suggested minimum drop-regimes on Day-1 were significantly different (120 drops ciprofloxacin, 34 drops ofloxacin, p < 0.0001), many of the published guidelines suggested the same drop-regime for both fluoroquinolones. The suggested drop numbers on Day-1 for ciprofloxacin in these guidelines and case studies were significantly less than those used in the clinical studies (p = 0.043). Increased treatment failure rates for ciprofloxacin are associated with lower drop numbers on Day-1. The Day-1 dosing rates for ciprofloxacin and ofloxacin should be considered separately, and the regimes suggested in published guidelines and case studies may need be re-considered in light of the findings of this review.