Association Between Rate of Ganglion Cell Complex Thinning and Rate of Central Visual Field Loss.

Importance: Whether rapid ganglion cell complex (GCC) thinning during an initial follow-up period is associated with rates of central visual field loss over time is unclear but important to understand because risk of glaucoma progression can help guide treatment intensity. Objective: To investigate the association between the rate of GCC thinning during initial follow-up and the rate of central visual field loss. Design, Setting, and Participants: This retrospective cohort study assessed patients older than 18 years with glaucoma at a tertiary glaucoma center who were followed up from June 18, 2014, to January 11, 2019. Data analysis for the current study was undertaken in March 2022. Main Outcomes and Measures: Initial rates of GCC thinning were obtained from global GCC thickness values of the first 3 optical coherence tomography (OCT) scans. Rates of central visual field loss were assessed as the change in central (10-2) visual field mean deviation during the 4.7-year follow-up period by univariable and multivariable linear mixed-effects models. Eyes were categorized as slow (>-1 µm/y) or fast (≤-1 µm/y) progressors based on rates of GCC thinning. Results: The cohort consisted of 202 eyes of 139 patients (mean [SD] age, 68.7 [10.0] years; 72 male [51.8%]); 44 African American patients (31.7%), 13 Asian patients (9.4%), 80 White patients (57.6%), and 2 patients who identified as other race and ethnicity (1.4%) were analyzed. The rate of GCC change was -0.56 µm/y (95% CI, -0.66 to -0.46 µm/y) during a mean initial follow-up of 1.8 years (95% CI, 1.7-2.0 years). A total of 163 eyes (80.7%) were slow OCT progressors, and 39 (19.3%) were fast OCT progressors, with rates of GCC thinning of -0.3 µm/y (95% CI, -0.4 to -0.2 µm/y) and -1.6 µm/y (-1.8 to -1.3 µm/y), respectively. The rates of 10-2 visual field mean deviation worsening among slow and fast OCT progressors were -0.10 dB/y (95% CI, -0.16 to 0.00 dB/y) and -0.34 dB/y (95% CI, -0.51 to -0.16 dB/y), respectively (difference, -0.26 dB/y; 95% CI, -0.45 to -0.07 dB/y; P = .008). Conclusions and Relevance: In this cohort study, rapid GCC thinning during an initial follow-up period was associated with faster rates of central visual field decline. These findings support use of longitudinal macular OCT scans assisting clinical decision-making for glaucoma and also may guide possible intensification of therapy in high-risk patients.

Vision-Related Quality of Life Among Healthy, Preperimetric Glaucoma, and Perimetric Glaucoma Patients.

PURPOSE: To investigate the association of vision-related quality of life (VRQOL) with the central visual field and macular ganglion cell complex (GCC) thickness in healthy control participants, patients with preperimetric glaucoma, and patients with perimetric glaucoma. DESIGN: Retrospective cross-sectional study. METHODS: A total of 39 healthy, 34 preperimetric glaucoma, and 145 perimetric glaucoma patients completed the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ). A linear mixed-effect models was used to investigate the association between the glaucoma stage as measured by binocular 10-2 visual field mean sensitivity (VFMS) and GCC thickness with the Rasch-calibrated NEI-VFQ score. RESULTS: A total of 436 eyes from 218 participants (mean age = 67.2 [95% CI = 65.1 to 69.2] years) were enrolled. VRQOL calculated by the NEI-VFQ Rasch-calibrated score was worst for patients with perimetric glaucoma (50.7 [95% CI = 47.2 to 54.2]), followed by patients with preperimetric glaucoma (41.2 [95% CI = 34.5 to 47.9]) and healthy controls (29.3 [95% CI = 24.0 to 34.7]. Worse VRQOL had a moderate association with a worse global binocular 10-2 VFMS (-3.4 [95% CI = -5.0 to -1.9] dB per 1 score; P < .001; adjusted R2 = 0.27), but not with a thinner global GCC in the better eye (-0.1 [95% CI = -0.2 to 0.1] µm per 1 score; P =.0485; adjusted R2 = 0.17). CONCLUSIONS: These findings suggest that patients with perimetric and preperimetric glaucoma have worse VRQOL than patients with healthy eyes. As compared to macular thickness measurements, the central visual field is more strongly associated with VRQOL and may better help to identify patients in need of intervention.

Detection of Nonglaucomatous Macula Findings With Ganglion Cell Analysis Printouts vs Full Macular Cube Scans.

Importance: Ganglion cell analysis (GCA) of ocular coherence tomography (OCT) imaging is routinely used to detect and monitor glaucomatous damage of the ganglion cell complex in the macula. The GCA printout provides qualitative and quantitative data about the macular ganglion cell-inner plexiform layer and a single B-scan of the retina through the fovea. However, the full macular cube scan, including all 128 B-scans, is available for review. The macular cube scan provides considerable information about nonglaucomatous ocular pathology that may be missed if clinicians review only the GCA printout. Objective: To determine the frequency and type of nonglaucomatous macular findings that are observable in the full macular cube scan but not the GCA printout. Design, Setting, and Participants: A retrospective cross-sectional analysis of GCA printouts and full macular cube scans to detect nonglaucomatous macular pathology at a tertiary care academic center. Consecutive patients undergoing ganglion cell complex imaging during routine glaucoma evaluations over a 1-week period in a multi-clinician glaucoma clinic. Main Outcomes and Measures: The prevalence and type of nonglaucomatous macular pathology visible on the GCA printout or macular cube scan. Results: Among 105 patients (mean (SD) age, 67 (15.46) years; 63 [60%] female and 42 [40%] male) 201 eyes were imaged (64 [31.7%] with suspected glaucoma, 126 [62.4%] with open-angle glaucoma, 6 [3.0%] with closed-angle glaucoma, and 6 [3.0%] with other glaucoma). GCA printouts and macular cube scans revealed nonglaucomatous macular pathology in 65 eyes (32.2%). Of these, 25 eyes (38.5%) included findings that were not visible on the GCA printout. Of the cases not visible on the printout, 16 eyes (64.0% ) included macular pathology that required further evaluation. Conclusions and Relevance: The findings indicate that nonglaucomatous macular pathology may be missed based on GCA printouts alone. While it may be beneficial to review the full macular cube to detect potentially vision-threatening disease and ensure proper patient care, this study cannot determine if this missed pathology affects clinical outcomes.

Association Between Ganglion Cell Complex Thinning and Vision-Related Quality of Life in Glaucoma.

Importance: Faster structural changes may be associated with worse vision-related quality of life in patients with glaucoma. Objectives: To evaluate the association between the rate of ganglion cell complex thinning and the Vision Function Questionnaire in glaucoma. Design, Setting, and Participants: This retrospective analysis of a longitudinal cohort was designed in October 2021. Patients were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Two hundred thirty-six eyes of 118 patients with diagnosed or suspected glaucoma were followed up with imaging for a mean of 4.1 years from September 2014 to March 2020. Main Outcomes and Measures: The Vision Function Questionnaire was evaluated using the 25-item National Eye Institute Visual Function at the last follow-up visit. Ganglion cell complex thickness was derived from macular optical coherence tomography scans and averaged within 3 circular areas (3.4°, 5.6°, and 6.8° from the fovea) and superior and inferior hemiregions. Linear mixed-effects models were used to investigate the association between the rate of ganglion cell complex thinning and Rasch-calibrated Vision Function Questionnaire score. Results: The mean (SD) age was 73.2 (8.7) years, 65 participants (55.1%) were female, and 53 participants (44.9%) were African American. Race was self-reported by the participants. Mean composite Rasch-calibrated National Eye Institute Visual Function Questionnaire score was 50.3 (95% CI, 45.9-54.6). A faster annual rate of global ganglion cell complex thinning in the better eye was associated with a higher disability reflected by the composite National Eye Institute Visual Function Questionnaire score (-15.0 [95% CI, -28.4 to -1.7] per 1 µm faster; P = .03). When stratified by degrees from the fovea, the 5.6° and 6.8° areas were associated with the composite National Eye Institute Visual Function Questionnaire Rasch-calibrated score (-14.5 [95% CI, -27.0 to -2.0] per 1 µm faster; R2 = 0.201; P = .03; and -23.7 [95% CI, -45.5 to -1.9] per 1 µm faster; R2 = 0.196; P = .02, respectively), and -8.0 (95% CI, -16.8 to 0.8) per 1 µm faster for the 3.4° area (R2 = 0.184; P = .07) after adjusting for confounding factors. Conclusions and Relevance: These findings suggest that faster and sectoral central location of ganglion cell complex thinning provides useful information in determining the risk of vision-related quality of life in glaucoma. Monitoring macular structure may be useful for determining the risk of functional impairment in glaucoma.

Dry Eye Symptom Severity and Visual Field Reliability Metrics.

PRCIS: Tracking failure frequency (TFF) increases with dry eye symptom severity and in the left eye. PURPOSE: Symptoms of dry eye disease are commonly encountered in glaucoma patients and can be exacerbated by topical glaucoma medications. Dry eye disease may influence the reliability of visual field (VF) tests and impact the accurate interpretation of the results. PATIENTS AND METHODS: Patients at the Veterans Administration Medical Center San Diego completed the 5-item Dry Eye Questionnaire before VF testing between December 2018 and February 2019. VF reliability metrics were recorded for each patient. Standard reliability metrics included fixation losses, false positive, and false negative rates. Gaze tracking (GT) metrics included percent of stimuli with gaze deviations between 1 and 2 degrees, 3 and 5 degrees, 6 degrees or greater, and percent of stimuli with tracking failure (TFF). The use of glaucoma medications and artificial tears was also recorded. RESULTS: A total of 494 patients completed the 5-item Dry Eye Questionnaire and VF testing. There was no association between dry eye symptom severity and standard reliability metrics or most GT metrics. However, TFF increased as dry eye symptom severity increased (P=0.015). TFF was also greater in the left eye, which was tested second (P=0.012); no other reliability metrics were related to laterality. Patients were more likely to use artificial tears with increased dry eye symptom severity (P<0.001), but there was no relationship between symptom severity and glaucoma medication use. DISCUSSION: Dry eye symptom severity may influence the acceptable range or threshold of TFF when using GT metrics to determine VF reliability. Likewise, the acceptable range or threshold for TFF may be different between eyes.

The First Epiretinal Implant for Hereditary Blindness in the Asia-Pacific Region.

In February 2013, the Argus® II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA, US) became the first "bionic eye" approved by the FDA to restore useful vision in patients previously blinded by end-stage retinitis pigmentosa, a hereditary, progressive degeneration of the outer retinal photoreceptor cells. The system captures and converts an external optical input into an electrical signal that activates an epiretinal electrode array on the inner surface of the retina. This signal bypasses dysfunctional photoreceptors and directly stimulates the functional inner retina, thus transmitting information to the visual cortex and creating artificial vision. This article describes the first implantation of the Argus II Retinal Prosthesis System in the Asia-Pacific region, which occurred in a deaf and blind 72-year-old Japanese American woman with Usher syndrome. At 57 months after her operation, the patient uses the device daily to perform visual tasks, and the microelectrode array remains in the proper position on the macula. This case demonstrates the long-term safety and efficacy of the Argus II epiretinal implant, which allowed a functionally blind patient to gain meaningful vision.

Prior infection with antigenically heterologous low pathogenic avian influenza viruses interferes with the lethality of the H5 highly pathogenic strain in domestic ducks.

Low and highly pathogenic avian influenza viruses (LPAIVs and HPAIVs, respectively) have been co-circulating in poultry populations in Asian, Middle Eastern, and African countries. In our avian-flu surveillance in Vietnamese domestic ducks, viral genes of LPAIV and HPAIV have been frequently detected in the same individual. To assess the influence of LPAIV on the pathogenicity of H5 HPAIV in domestic ducks, an experimental co-infection study was performed. One-week-old domestic ducks were inoculated intranasally and orally with phosphate-buffered saline (PBS) (control) or 106 EID50 of LPAIVs (A/duck/Vietnam/LBM678/2014 (H6N6) or A/Muscovy duck/Vietnam/LBM694/2014 (H9N2)). Seven days later, these ducks were inoculated with HPAIV (A/Muscovy duck/Vietnam/LBM808/2015 (H5N6)) in the same manner. The respective survival rates were 100% and 50% in ducks pre-infected with LBM694 or LBM678 strains and both higher than the survival of the control group (25%). The virus titers in oral/cloacal swabs of each LPAIV pre-inoculation group were significantly lower at 3-5 days post-HPAIV inoculation. Notably, almost no virus was detected in swabs from surviving individuals of the LBM678 pre-inoculation group. Antigenic cross-reactivity among the viruses was not observed in the neutralization test. These results suggest that pre-infection with LPAIV attenuates the pathogenicity of HPAIV in domestic ducks, which might be explained by innate and/or cell-mediated immunity induced by the initial infection with LPAIV.

Differentiating Exudative Macular Degeneration and Polypoidal Choroidal Vasculopathy Using OCT B-Scan.

PURPOSE: Although polypoidal choroidal vasculopathy (PCV) is best diagnosed with indocyanine green angiography (ICGA), ICGA is often unavailable or not ordered. OCT is widely available, and OCT B-scan can visualize polypoidal lesions diagnostic of PCV as inverted U-shaped elevations of the retinal pigment epithelium (RPE) with heterogeneous reflectivity and sometimes ring-shaped lesions within the polypoidal lesion. This study aims to differentiate findings between eyes diagnosed with PCV or typical exudative age-related macular degeneration (AMD) using ICGA and then compares findings noted on the OCT B-scan line scan in each group. DESIGN: Retrospective, chart review. METHODS: Clinical features of eyes with PCV and typical exudative AMD were compared by using ICGA. Eyes with PCV were evaluated for inverted U-shaped polypoidal lesions, which are the main differentiating finding of PCV from typical exudative AMD. Data collected included presence of subretinal fluid (SRF), macular edema or intraretinal edema, subretinal hyperreflective material (SHRM), and retinal pigment epithelial detachment (RPED). These findings were evaluated in 2 parts: baseline and after 6 to 9 months of antiangiogenic therapy. Additionally, analysis was performed for the presence of polypoidal lesions before and after treatment. MAIN OUTCOME MEASURES: Presence of inverted U-shaped lesions on OCT B-scan following treatment. RESULTS: A total of 112 eyes of 106 patients were included. A total of 69 eyes were diagnosed with PCV, and 43 eyes were diagnosed with typical exudative AMD. Compared with AMD eyes, PCV eyes had an increased prevalence of SRF at baseline and after 6 to 9 months of treatment, but the prevalence of macular edema, SHRM, and RPED was similar at baseline and at 6 to 9 months after treatment. In PCV eyes, the presence of visible polypoidal lesions decreased from 56.5% to 24.6% after treatment. CONCLUSIONS: If PCV is suspected in an anti-vascular endothelial growth factor (VEGF)-resistant case of exudative AMD, in the absence of ICGA availability, it is important to look at the baseline OCT B-scan before therapy for evidence of polypoidal lesions. The characteristic inverted U-shaped elevation was present in more than half of PCV eyes on OCT B-scan at baseline but disappeared after antiangiogenic therapy in 56.4% of cases in which this was initially identified. Subretinal fluid was more prevalent in PCV eyes than non-PCV AMD eyes.

Introducing the 24-2C Visual Field Test in Neuro-Ophthalmology.

PURPOSE: The Humphrey 24-2C visual field test is a modified 24-2 visual field test that incorporates 10 additional test points in the central 10° of vision. This study compares the new 24-2C test to the standard Humphrey 10-2 visual field test in patients presenting for neuro-ophthalmology evaluation to evaluate its ability to detect central visual field defects. METHODS: Twenty-five neuro-ophthalmology patients (42 eyes) underwent both 24-2C and 10-2 visual field testing using the Humphrey perimeter. The number of flagged total deviation (TD) and pattern deviation (PD) points of the 10 added test points of the 24-2C were compared with the corresponding 10-2 fields at the P < 5%, P < 2%, and P < 1% significance levels. The total number of flagged TD points were further analyzed by diagnosis. An experienced neuro-ophthalmologist evaluated all visual fields, commenting on the added value for clinical practice. RESULTS: There was no significant difference between the number of flagged TD and PD points of the 10 extra 24-2C points and corresponding 10-2 points at all significance levels. When analyzed by diagnosis, there was no significant difference in the number of flagged TD points in patients with optic neuritis, ischemic optic neuropathy, optic atrophy, and no neuro-ophthalmic disease. The added 24-2C points aided in identifying visual field defects and areas of spared central vision and had similar diagnostic value as the 10-2. CONCLUSIONS: The 24-2C is able to detect visual field loss in the central 10° that corroborates with loss detected in the 10-2 pattern. The 24-2C exhibits potential to be used as a hybrid between the 24-2 and 10-2 to better evaluate visual field defects.

INVOLUTION OF NEOVASCULAR AGE-RELATED MACULAR DEGENERATION AFTER ENDOPHTHALMITIS.

PURPOSE: To report patients who demonstrated an alteration in the clinical and optical coherence tomography features of neovascular age-related macular degeneration after resolution of endophthalmitis. METHODS: Retrospective case series of the subsequent changes in the macula and need for anti-vascular endothelial growth factor therapy in patients with neovascular age-related macular degeneration who developed endophthalmitis after intravitreal injection. RESULTS: The study included seven eyes of seven patients with follow-up ranging between 3 months and 11 years. The vitreous cultures (n = 7) before intravitreal antibiotic injection were the following: culture-negative (4) and coagulase-negative Staphylococcus (3). Initial treatment included vitreous tap and injection (4) and pars plana vitrectomy (3). In 5/7 eyes, the optical coherence tomography showed resolution of subretinal fluid and serous pigment epithelial detachment, and there was no additional anti-vascular endothelial growth factor treatment administered. CONCLUSION: After successful treatment of endophthalmitis in patients with neovascular age-related macular degeneration, there was relative involution of the maculopathy and reduced anti-vascular endothelial growth factor treatment burden in this series.

Tonic pupil caused by adenoid cystic carcinoma versus postradiation changes to the ciliary ganglion.

A tonic pupil, without other features of an oculomotor neuropathy, is due to a lesion in the ciliary ganglion or short ciliary nerves. Here, we present a case of a tonic pupil in a woman with radiation-treated adenoid cystic carcinoma of the nasopharynx with perineural spread and skull base involvement. This a rare case of a tonic pupil caused by direct invasion of the ciliary ganglion or postradiation effects.

Correlating Ophthalmology Exposure in Medical School to Applying and Matching Into an Ophthalmology Residency.

PURPOSE: To correlate ophthalmology curricular exposure in medical school to the number of students who applied and matched into ophthalmology residency programs. Given the high curricular burden placed on medical schools, the authors sought to better characterize existing ophthalmology curricula and to delineate which offerings are closely related to high numbers of students applying and matching into ophthalmology residencies. METHOD: The authors reviewed the extent of ophthalmology curricula between 2007 and 2017 via a survey administered in 2018 to all U.S. Association of American Medical Colleges (AAMC)-affiliated medical schools. They obtained residency application and match data with permission from the Association of University Professors of Ophthalmology. The authors compared metrics of ophthalmology exposure with the number of students who applied and matched into ophthalmology during the corresponding year using mixed-effects Poisson regression analysis. RESULTS: This study includes 49 U.S. AAMC-affiliated medical schools. When adjusted for the number of applicants per year, the following were significantly (P < .05) associated with matching into an ophthalmology residency: the presence of an ophthalmology department, an ophthalmology residency program, an ophthalmology interest group, ophthalmologists on faculty, ophthalmology content in the preclinical curriculum, preclinical lectures taught by ophthalmologists, and the availability of an optional fourth-year ophthalmology elective. Multivariable analysis indicated both that the presence of an ophthalmology residency program was the only independent predictor of matching into an ophthalmology residency and that the presence of an ophthalmology residency program, ophthalmology content in the preclinical curriculum, and preclinical lectures taught by ophthalmologists are independent predictors for applying. CONCLUSIONS: A foundation in ophthalmology is crucial for all physicians, especially those who may encounter patients with eye problems in emergency or primary care settings. However, for those students considering a career in ophthalmology, choosing a medical school with an ophthalmology department and residency program is particularly important.

Two differing presentations of periocular dermatitis as a side effect of dupilumab for atopic dermatitis.

Dupilumab is a monoclonal antibody used to treat atopic dermatitis. Worsening of atopic dermatitis and conjunctivitis following dupilumab use are reported adverse effects; however, there is little reported on the nature and mechanism of these complications. Here, we describe two patients with chronic atopic dermatitis who developed new or severely worsened periocular dermatitis, believed to be a side effect of dupilumab injections, and resolution after its discontinuation. We explore the possibility of dupilumab-induced suppression of Th2 mediated inflammation and upregulation of Th1 and IFNγ mediated inflammation as a possible mechanism.

Pulmonary hemosiderosis in children with bronchopulmonary dysplasia.

We describe a possible association between pulmonary hemosiderosis (PH) and a history of bronchopulmonary dysplasia (BPD). Both patients were born at 28-week gestation and presented with PH at ages 22 months and 6 years, respectively. Both initially presented with cough and tachypnea, and bronchoalveolar lavage showed evidence of hemosiderin-laden macrophages. Initial hemoglobin levels were < 4 g/dL and chest radiographs showed diffuse infiltrates that cleared dramatically within days after initiation of intravenous corticosteroids. In the first case, frank pulmonary blood was observed upon initial intubation, prompting the need for high frequency ventilation, immediate corticosteroids, and antibiotics. The mechanical ventilation wean was made possible by the addition of mycophenolate mofetil (MMF) and hydroxychloroquine. Slow tapering off of medications was accomplished over 6 years. These cases represent a possible correlation between prematurity-associated BPD and PH. We present a review of the literature regarding this possible association. In addition, MMF proved to be life-saving in one of the PH cases, as it has been in pulmonary hemorrhage related to systemic lupus erythematosus. Further studies are warranted to investigate the possible association between PH and prematurity-related BPD, as well as the use of MMF in the treatment of PH.

A pediatric residency research requirement to improve collaborative resident and faculty publication productivity.

Involvement in a research project can teach training physicians about the scientific process involved in medicine. For this reason, the University of Hawai'i pediatrics department developed a Residency Research Requirement and Program (RRRP) in 2001. We studied a 14-year time period before and after the RRRP was initiated, and found a greater then ten-fold increase in resident publications and faculty involvement in these projects. Many of these manuscripts were the result of resident collaboration and this also increased significantly. The residents who later went into fellowship training were found to be more likely to publish their work. An RRRP encourages residents and faculty to become involved in research publications and other scholarly activities. Its development may help to motivate training physicians to learn important research skills.