Validating the Generalizability of Ophthalmic Artificial Intelligence Models on Real-World Clinical Data.

Purpose: This study aims to investigate generalizability of deep learning (DL) models trained on commonly used public fundus images to an instance of real-world data (RWD) for glaucoma diagnosis. Methods: We used Illinois Eye and Ear Infirmary fundus data set as an instance of RWD in addition to six publicly available fundus data sets. We compared the performance of DL-trained models on public data and RWD for glaucoma classification and optic disc (OD) segmentation tasks. For each task, we created models trained on each data set, respectively, and each model was tested on both data sets. We further examined each model's decision-making process and learned embeddings for the glaucoma classification task. Results: Using public data for the test set, public-trained models outperformed RWD-trained models in OD segmentation and glaucoma classification with a mean intersection over union of 96.3% and mean area under the receiver operating characteristic curve of 95.0%, respectively. Using the RWD test set, the performance of public models decreased by 8.0% and 18.4% to 85.6% and 76.6% for OD segmentation and glaucoma classification tasks, respectively. RWD models outperformed public models on RWD test sets by 2.0% and 9.5%, respectively, in OD segmentation and glaucoma classification tasks. Conclusions: DL models trained on commonly used public data have limited ability to generalize to RWD for classifying glaucoma. They perform similarly to RWD models for OD segmentation. Translational Relevance: RWD is a potential solution for improving generalizability of DL models and enabling clinical translations in the care of prevalent blinding ophthalmic conditions, such as glaucoma.

Use of Immunosuppression and the Risk of Subsequent Overall or Cancer Mortality.

PURPOSE: To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression. DESIGN: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression. PARTICIPANTS: Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer. METHODS: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study. MAIN OUTCOME MEASURES: Overall mortality and CM. RESULTS: Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio [SMR] = 0.95, 95% confidence interval [CI], 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR = 1.04, 95% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio [aHR] = 0.88, 0.89, 0.90, 1.11) and CM (aHR = 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration. CONCLUSIONS: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A Platform for Tracking Surgeon and Observer Gaze as a Surrogate for Attention in Ophthalmic Surgery.

Purpose: To develop and validate a platform that can extract eye gaze metrics from surgeons observing cataract and vitreoretinal procedures and to enable post hoc data analysis to assess potential discrepancies in eye movement behavior according to surgeon experience. Design: Experimental, prospective, single-center study. Participants: Eleven ophthalmic surgeons observing deidentified vitreoretinal and cataract surgical procedures performed at a single university-based medical center. Methods: An open-source platform was developed to extract gaze coordinates and metrics from ophthalmic surgeons via a computer vision algorithm in conjunction with a neural network to track and segment instruments and tissues, identifying areas of attention in the visual field of study subjects. Eleven surgeons provided validation data by watching videos of 6 heterogeneous vitreoretinal and cataract surgical phases. Main Outcome Measures: Accuracy and distance traveled by the eye gaze of participants and overlap of the participants' eye gaze with instruments and tissues while observing surgical procedures. Results: The platform demonstrated repeatability of > 94% when acquiring the eye gaze behavior of subjects. Attending ophthalmic surgeons and clinical fellows exhibited a lower overall cartesian distance traveled in comparison to resident physicians in ophthalmology (P < 0.02). Ophthalmology residents and clinical fellows exhibited more fixations to the display area where surgical device parameters were superimposed than attending surgeons (P < 0.05). There was a trend toward gaze overlap with the instrument tooltip location among resident physicians in comparison to attending surgeons and fellows (41.42% vs. 34.8%, P > 0.2). The number and duration of fixations did not vary substantially among groups (P > 0.3). Conclusions: The platform proved effective in extracting gaze metrics of ophthalmic surgeons. These preliminary data suggest that surgeon gaze behavior differs according to experience.

Feature Tracking and Segmentation in Real Time via Deep Learning in Vitreoretinal Surgery: A Platform for Artificial Intelligence-Mediated Surgical Guidance.

PURPOSE: This study investigated whether a deep-learning neural network can detect and segment surgical instrumentation and relevant tissue boundaries and landmarks within the retina using imaging acquired from a surgical microscope in real time, with the goal of providing image-guided vitreoretinal (VR) microsurgery. DESIGN: Retrospective analysis via a prospective, single-center study. PARTICIPANTS: One hundred and one patients undergoing VR surgery, inclusive of core vitrectomy, membrane peeling, and endolaser application, in a university-based ophthalmology department between July 1, 2020, and September 1, 2021. METHODS: A dataset composed of 606 surgical image frames was annotated by 3 VR surgeons. Annotation consisted of identifying the location and area of the following features, when present in-frame: vitrector-, forceps-, and endolaser tooltips, optic disc, fovea, retinal tears, retinal detachment, fibrovascular proliferation, endolaser spots, area where endolaser was applied, and macular hole. An instance segmentation fully convolutional neural network (YOLACT++) was adapted and trained, and fivefold cross-validation was employed to generate metrics for accuracy. MAIN OUTCOME MEASURES: Area under the precision-recall curve (AUPR) for the detection of elements tracked and segmented in the final test dataset; the frames per second (FPS) for the assessment of suitability for real-time performance of the model. RESULTS: The platform detected and classified the vitrector tooltip with a mean AUPR of 0.972 ± 0.009. The segmentation of target tissues, such as the optic disc, fovea, and macular hole reached mean AUPR values of 0.928 ± 0.013, 0.844 ± 0.039, and 0.916 ± 0.021, respectively. The postprocessed image was rendered at a full high-definition resolution of 1920 × 1080 pixels at 38.77 ± 1.52 FPS when attached to a surgical visualization system, reaching up to 87.44 ± 3.8 FPS. CONCLUSIONS: Neural Networks can localize, classify, and segment tissues and instruments during VR procedures in real time. We propose a framework for developing surgical guidance and assessment platform that may guide surgical decision-making and help in formulating tools for systematic analyses of VR surgery. Potential applications include collision avoidance to prevent unintended instrument-tissue interactions and the extraction of spatial localization and movement of surgical instruments for surgical data science research. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Open globe injuries from projectile impact: Initial presentation and outcomes.

PURPOSE: To describe the characteristics and correlates of open globe injuries secondary to projectile injury and outcomes following surgical open globe repair at an urban tertiary referral center. METHODS: Records of all patients with a history of open globe injury secondary to projectile injury and surgical open globe at a tertiary referral hospital between January 1, 2010 and December 31, 2016 were reviewed. Demographics, type of trauma, wound extent, presence of foreign body, and presenting clinical findings are reported. Outcomes for patients with greater than 6 months of follow-up included additional surgeries, final visual acuity, and clinical findings. RESULTS: Of 214 patients who underwent open globe repair, 73 (34.1%) were due to projectile impact. Mean age was 37.9 years and patients were primarily male (n = 66, P < 0.001). Most injuries resulted in globe laceration (68.5%, P < 0.001), and wound extent was zone 1 (45.2%), zone 2 (20.5%), zone 3 (27.4%), or unknown (6.8%). Associated findings included foreign body (35.6%) and orbital fracture (15%). Of 41 patients with at least 6 months of follow-up, 70% had additional surgeries following their initial surgical repair. Laceration injuries tended to be more anterior (P = 0.002) with better visual outcomes (P = 0.045) than those with globe rupture, and concomitant orbital fracture associated with poor visual outcomes. Overall, 58.5% of patients had 20/40 or better final best-corrected visual acuity. CONCLUSION: This is the largest report of open globe injury due to projectile impact. Visual prognosis in this population is very good, with most patients achieving better than 20/40 vision in our study.

Evaluation of Artificial Intelligence-Based Intraoperative Guidance Tools for Phacoemulsification Cataract Surgery.

IMPORTANCE: Complications that arise from phacoemulsification procedures can lead to worse visual outcomes. Real-time image processing with artificial intelligence tools can extract data to deliver surgical guidance, potentially enhancing the surgical environment. OBJECTIVE: To evaluate the ability of a deep neural network to track the pupil, identify the surgical phase, and activate specific computer vision tools to aid the surgeon during phacoemulsification cataract surgery by providing visual feedback in real time. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study evaluated deidentified surgical videos of phacoemulsification cataract operations performed by faculty and trainee surgeons in a university-based ophthalmology department between July 1, 2020, and January 1, 2021, in a population-based cohort of patients. EXPOSURES: A region-based convolutional neural network was used to receive frames from the video source and, in real time, locate the pupil and in parallel identify the surgical phase being performed. Computer vision-based algorithms were applied according to the phase identified, providing visual feedback to the surgeon. MAIN OUTCOMES AND MEASURES: Outcomes were area under the receiver operator characteristic curve and area under the precision-recall curve for surgical phase classification and Dice score (harmonic mean of the precision and recall [sensitivity]) for detection of the pupil boundary. Network performance was assessed as video output in frames per second. A usability survey was administered to volunteer cataract surgeons previously unfamiliar with the platform. RESULTS: The region-based convolutional neural network model achieved area under the receiver operating characteristic curve values of 0.996 for capsulorhexis, 0.972 for phacoemulsification, 0.997 for cortex removal, and 0.880 for idle phase recognition. The final algorithm reached a Dice score of 90.23% for pupil segmentation and a mean (SD) processing speed of 97 (34) frames per second. Among the 11 cataract surgeons surveyed, 8 (72%) were mostly or extremely likely to use the current platform during surgery for complex cataract. CONCLUSIONS AND RELEVANCE: A computer vision approach using deep neural networks was able to pupil track, identify the surgical phase being executed, and activate surgical guidance tools. These results suggest that an artificial intelligence-based surgical guidance platform has the potential to enhance the surgeon experience in phacoemulsification cataract surgery. This proof-of-concept investigation suggests that a pipeline from a surgical microscope could be integrated with neural networks and computer vision tools to provide surgical guidance in real time.

Frequency of Urgent or Emergent Vitreoretinal Surgical Procedures in the United States During the COVID-19 Pandemic.

Importance: The American Academy of Ophthalmology (AAO) indicated that urgent or emergent vitreoretinal surgical procedures should continue during the coronavirus disease 2019 (COVID-19) pandemic. Although decreases in the frequency of critical procedures have been reported outside the field of ophthalmology, analyses are limited by volume, geography, and time. Objective: To evaluate whether the frequency of ophthalmic surgical procedures deemed urgent or emergent by the AAO changed across the United States during the COVID-19 pandemic. Design, Setting, and Participants: Vitreoretinal practices from 17 institutions throughout the US participated in this multicenter cross-sectional study. The frequency of 11 billed vitreoretinal Current Procedural Terminology (CPT) codes across respective weeks was obtained from each practice between January 1, 2019, and May 31, 2020. Data were clustered into intravitreal injections (code 67028), lasers and cryotherapy (codes 67141, 67145, and 67228), retinal detachment (RD) repairs (codes 67107, 67108, 67110, and 67113), and other vitrectomies (codes 67036, 67039, and 67040). Institutions were categorized by region (Northeast, Midwest, South, and West Coast), practice setting (academic [tax-exempt] or private [non-tax-exempt]), and date of respective statewide stay-at-home orders. Main Outcomes and Measures: Nationwide changes in the frequency of billing for urgent or emergent vitreoretinal surgical procedures during the COVID-19 pandemic. Results: A total of 526 536 CPT codes were ascertained: 483 313 injections, 19 257 lasers or cryotherapy, 14 949 RD repairs, and 9017 other vitrectomies. Relative to 2019, a weekly institutional decrease in injections was observed from March 30 to May 2, 2020, with a maximal 38.6% decrease (from a mean [SD] of 437.8 [436.3] to 273.8 [269.0] injections) from April 6 to 12, 2020 (95% CI, -259 to -69 injections; P = .002). A weekly decrease was also identified that spanned a longer interval, at least until study conclusion (March 16 to May 31, 2020), for lasers and cryotherapy, with a maximal 79.6% decrease (from a mean [SD] of 6.6 [7.7] to 1.5 [2.0] procedures) from April 6 to 12, 2020 (95% CI, -6.8 to -3.3 procedures; P < .001), for RD repairs, with a maximal 59.4% decrease (from a mean [SD] of 3.5 [4.0] to 1.6 [2.2] repairs) from April 13 to 19, 2020 (95% CI, -2.7 to -1.4 repairs; P < .001), and for other vitrectomies, with a maximal 84.3% decrease (from a mean [SD] of 3.0 [3.1] to 0.4 [0.8] other vitrectomies) from April 6 to 12, 2020 (95% CI, -3.3 to -1.8 other vitrectomies; P < .001). No differences were identified by region, setting, or state-level stay-at-home order adjustment. Conclusions and Relevance: Although the AAO endorsed the continued performance of urgent or emergent vitreoretinal surgical procedures, the frequency of such procedures throughout the country experienced a substantial decrease that may persist after the COVID-19 pandemic's initial exponential growth phase. This decrease appears independent of region, setting, and state-level stay-at-home orders. It is unknown to what extent vitreoretinal intervention would have decreased without AAO recommendations, and how the decrease is associated with outcomes. Although safety is paramount during the COVID-19 pandemic, practices should consider prioritizing availability for managing high-acuity conditions until underlying reasons for the reduction are fully appreciated.

Visual Rehabilitation With Contact Lenses Following Open Globe Trauma.

OBJECTIVES: To describe visual outcomes with various contact lens modalities in patients with a history of ocular trauma who underwent surgical open globe repair. METHODS: Records of all patients with a history of open globe injury and repair at a tertiary care hospital between January 1, 2010, and December 31, 2016, were reviewed. Demographics, type of injury, and visual acuity were assessed before and after contact lens evaluation. RESULTS: Of 214 patients who underwent open globe repair, 29 (13.6%) were evaluated with a contact lens. Visual acuity improved in 97% (28 of 29) of patients from 1.47±0.75 to 0.67±0.71 logarithm of the minimal angle of resolution (logMAR) with manifest refraction to 0.28±0.45 logMAR with contact lenses (n=29; P<0.0001). Corneal opacity was the most common clinical indication (20 of 29) for fitting followed by aphakia (13 of 29). A range of contact lens modalities, including corneal rigid gas-permeable (12 of 28), soft (9 of 28), hybrid (3 of 28), scleral gas-permeable (2 of 28), and piggyback (2 of 28) lenses were prescribed. CONCLUSION: In this study, patients with a history of trauma and open globe repair with good neurosensory visual potential had improvements in visual acuity with contact lens greater than manifest refraction. Soft and gas-permeable lenses were used to improve visual acuity in patients with a history of open globe repair and corneal scarring, aphakia, iris abnormalities, or other ocular sequelae. Although corneal rigid gas-permeable lenses were prescribed most often, additional consideration should be given to other contact lens modalities, including soft, piggyback, hybrid, and scleral gas-permeable lenses.

Design of a navigational catheter system for the targeted delivery of therapeutics within the suprachoroidal space.

Diseases of the posterior segment of the eye are common causes of blindness and can be difficult to treat due to their location. Recently, there has been increased interest in the use of the suprachoroidal space to deliver therapeutics to the posterior segment. This space is accessible through a trans-scleral approach and blunt dissection of the adjacent scleral and choroidal tissues. However, despite recent commercial interest, there are few tools designed specifically to provide targeted delivery of therapeutics to a localised region within the suprachoroidal space. Therefore, we designed and prototyped a novel navigational catheter system for the targeted delivery of payloads within the suprachoroidal space. The system consists of a customised catheter tip designed to minimise blunt dissection stresses on neighbouring tissues, a mechanism for controlled catheter navigation, and a method for targeted delivery of large payloads. A customised in vitro model of the eye was also designed to visually demonstrate the capability of the catheter system to controllably navigate within the suprachoroidal space and deliver a targeted payload. This system can enable the delivery of large therapeutic payloads to the eye for the treatment of posterior eye diseases, thereby impacting the development and availability of vision-saving treatments.

Safety and Efficacy of Subretinally Administered Palucorcel for Geographic Atrophy of Age-Related Macular Degeneration: Phase 2b Study.

PURPOSE: To evaluate safety and successful use of a novel subretinal delivery system and suprachoroidal surgical approach and safety and activity of human umbilical tissue-derived cells (palucorcel) via a novel delivery system in patients with geographic atrophy (GA). DESIGN: Multicenter, open-label phase 2b study. PARTICIPANTS: Participants were 55 to 90 years with GA secondary to age-related macular degeneration (AMD) and best-corrected visual acuity (BCVA) of 20/80 to 20/800. Exclusion criteria included neovascular AMD in the intervention eye, glaucoma with intraocular pressure of 25 mmHg or more, or other significant ophthalmologic conditions. METHODS: Participants received a subretinal injection of palucorcel, 3.0 × 105 cells in 50 µl, using the custom-designed delivery system and surgical procedure. MAIN OUTCOME MEASURES: Safety assessments included treatment-emergent adverse events (AEs), immunologic assessments, and ophthalmologic evaluations. Efficacy was evaluated as change in mean number of BCVA letters from baseline, proportion of participants gaining 15 BCVA letters or more, and growth rate of GA lesions at 12 months. RESULTS: Surgery and palucorcel administration were performed in 21 participants at 8 sites by 8 different surgeons. At baseline, median total area of GA was 13.4 mm2 and median BCVA was 43 letters in the intervention eye. Eye-related AEs occurred in 76% of participants (16/21), including conjunctival hemorrhage (n = 5), retinal hemorrhage (n = 4), and vitreous floaters (n = 4). Most AEs were mild and resolved within 1 month. No serious AEs, no retinal detachment or perforation, and no significant changes in intraocular pressure occurred. At month 12, mean change in BCVA from baseline was -5.9 letters correct (standard deviation, 13.0 letters correct) in the intervention eye and -3.7 letters correct (standard deviation, 9.0 letters correct) in the fellow eye. No participants showed improvement of 15 letters or more in the intervention eye, and 3 participants lost more than 15 letters by month 1. No apparent effect of treatment was observed. CONCLUSIONS: Palucorcel was delivered successfully to the targeted subretinal site using a novel delivery system and suprachoroidal approach for most participants; however, improvement in GA area, retardation of growth, or visual acuity were not demonstrated.

AMPLITUDE LOSS OF THE HIGH-FREQUENCY FLICKER ELECTRORETINOGRAM IN EARLY DIABETIC RETINOPATHY.

PURPOSE: To evaluate retinal dysfunction in diabetic patients who have mild or no nonproliferative diabetic retinopathy (DR) using the high-frequency flicker electroretinogram. METHODS: Light-adapted flicker electroretinograms were recorded from 15 diabetic patients who have no clinically apparent retinopathy, 15 diabetic patients who have mild nonproliferative DR, and 15 nondiabetic, age-equivalent controls. Electroretinograms were elicited by full-field flicker at 2 temporal frequencies, 31.25 and 62.5 Hz, and were recorded using conventional techniques. Amplitude and timing of the flicker responses were compared among the groups and correlated with clinical characteristics including age, acuity, disease duration, and HbA1c. RESULTS: The 31.25-Hz flicker amplitude was slightly, but nonsignificantly, smaller for subjects with no DR and mild nonproliferative DR , compared with the control group (both t < 1.38, P > 0.31); small, nonsignificant response delays for both patient groups were also observed (both t < 1.57, P > 0.12). By contrast, there were significant amplitude reductions for the 62.5-Hz flicker stimulus: mean amplitude was reduced by 32% for subjects with no DR and by 41% for subjects with mild nonproliferative DR (both t > 2.92 and P < 0.01). Response timing at 62.5 Hz did not differ significantly from control for either group (both t < 1.2 and P > 0.39). Electroretinogram amplitude and timing were not correlated significantly with clinical characteristics. CONCLUSION: The 62.5-Hz flicker electroretinogram is useful for evaluating retinal dysfunction in diabetic patients who have mild or no DR because this response can be significantly reduced. Attenuation of the high-frequency flicker electroretinogram, which is primarily generated by bipolar cells, suggests a relatively early retinal site of neural dysfunction.

Epidemiological trends in 1452 cases of retinoblastoma from the Surveillance, Epidemiology, and End Results (SEER) registry.

OBJECTIVE: To assess retinoblastoma epidemiological trends in the Surveillance, Epidemiology, and End Results (SEER) registry. METHODS: All cases of retinoblastoma in the SEER database from 1973 to 2009 were identified. Kaplan-Meier survival analyses were performed for pathological grade, patient age, sex, year of diagnosis, and treatment modality. Cox proportional hazards regression assessed the impact of patient and tumour characteristics on survival. RESULTS: 1452 cases of retinoblastoma were analyzed. The mean patient age at diagnosis was 1.44 years. The tumour was unilateral in 71.0% and bilateral in 29.0%. The mean follow-up was 129.1 months. Overall survival increased during the study interval. Patients with bilateral tumours were diagnosed at an earlier age (0.46 years) than patients with unilateral disease (1.77 years; p < 0.0001). Bilateral retinoblastoma (90.3% 10-year overall survival) was associated with decreased overall survival than unilateral retinoblastoma (96.1% 10-year overall survival). Bilateral retinoblastoma was also associated with an increased incidence of nonocular malignancies (7.8%) compared with unilateral retinoblastoma (1.3%; p < 0.0001). Grade 1 tumours were diagnosed at a younger age (0.94 years) than grade 3 (2.24 years) and grade 4 tumours (2.14 years; p < 0.0001). Lower grade and lower stage tumours were independently associated with increased survival. In multivariate Cox proportional hazards analysis, T stage and laterality were the only covariates that correlated with overall survival. CONCLUSIONS: There appear to be associations between retinoblastoma tumour features such as tumour stage, pathological grade, and laterality with patient characteristics such as age at diagnosis, overall survival, and second malignancies.

Pupillary responses in non-proliferative diabetic retinopathy.

The goal of this study was to determine the extent of rod-, cone-, and melanopsin-mediated pupillary light reflex (PLR) abnormalities in diabetic patients who have non-proliferative diabetic retinopathy (NPDR). Fifty diabetic subjects who have different stages of NPDR and 25 age-equivalent, non-diabetic controls participated. PLRs were measured in response to full-field, brief-flash stimuli under conditions that target the rod, cone, and intrinsically-photosensitive (melanopsin) retinal ganglion cell pathways. Pupil responses were compared among the subjects groups using age-corrected linear mixed models. Compared to control, the mean baseline pupil diameters were significantly smaller for all patient groups in the dark (all p < 0.001) and for the moderate-severe NPDR group in the light (p = 0.003). Pairwise comparisons indicated: (1) the mean melanopsin-mediated PLR was significantly reduced in the mild and moderate-severe groups (both p < 0.001); (2) the mean cone-mediated PLR was reduced significantly in the moderate-severe group (p = 0.008); (3) no significant differences in the mean rod-mediated responses. The data indicate abnormalities in NPDR patients under conditions that separately assess pupil function driven by different photoreceptor classes. The results provide evidence for compromised neural function in these patients and provide a promising approach for quantifying their neural abnormalities.

The Effects of Diabetic Retinopathy Stage and Light Flicker on Inner Retinal Oxygen Extraction Fraction.

PURPOSE: We determined the effects of light flicker and diabetic retinopathy (DR) stage on retinal vascular diameter (D), oxygen saturation (SO2), and inner retinal oxygen extraction fraction (OEF). METHODS: Subjects were categorized as nondiabetic control (NC, n = 42), diabetic with no clinical DR (NDR; n = 32), nonproliferative DR (NPDR; n = 42), or proliferative DR (PDR; n = 14). Our customized optical imaging system simultaneously measured arterial and venous D (DA, DV) and SO2 (SO2A, SO2V) before and during light flicker. Inner retinal OEF was derived from SO2 values. Light flicker-induced ratios of metrics (DAR, DVR, SO2AR, SO2VR, OEFR) were calculated. RESULTS: Arterial D was larger in NPDR compared to NC (P = 0.01) and PDR (P = 0.002), whereas DV was similar among groups (P ≥ 0.16). Light flicker increased DA and DV (P ≤ 0.004), but DAR and DVR were similar among groups (P ≥ 0.09). Arterial SO2 was higher in all groups compared to NC (P ≤ 0.02) and higher in PDR compared to NDR and NPDR (P<0.001). Arterial SO2 did not change with light flicker (P ≥ 0.1). Venous SO2 was higher in NPDR and PDR compared to NC and NDR (P ≤ 0.02). Light flicker increased SO2V in NC, NDR, and PDR (P ≤ 0.003), and SO2VR was lower in NPDR compared to NC and NDR (P ≤ 0.05). Inner retinal OEF was lower in NPDR compared to NDR and PDR (P ≤ 0.02). Light flicker decreased OEF (P ≤ 0.03), but OEFR was greater in NPDR compared to NC and NDR (P ≤ 0.03). CONCLUSIONS: The findings of alterations in retinal D, SO2, OEF, and their light flicker-induced responses at stages of DR may be useful to elucidate the pathophysiology of DR.

Alterations in Retinal Layer Thickness and Reflectance at Different Stages of Diabetic Retinopathy by En Face Optical Coherence Tomography.

PURPOSE: This article reports a method for en face optical coherence tomography (OCT) imaging and quantitative assessment of alterations in both thickness and reflectance of individual retinal layers at different stages of diabetic retinopathy (DR). METHODS: High-density OCT raster volume scans were acquired in 29 diabetic subjects divided into no DR (NDR) or non-proliferative DR (NPDR) groups and 22 control subjects (CNTL). A customized image segmentation method identified eight retinal layer interfaces and generated en face thickness maps and reflectance images for nerve fiber layer (NFL), ganglion cell and inner plexiform layers (GCLIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor outer segment layer (OSL), and retinal pigment epithelium (RPE). Mean thickness and intensity values were calculated in nine macular subfields for each retinal layer. RESULTS: En face thickness maps and reflectance images of retinal layers in CNTL subjects corresponded to normal retinal anatomy. Total retinal thickness correlated negatively with age in nasal subfields (R ≤-0.31; P ≤ 0.03, N = 51). In NDR subjects, NFL and OPL thickness were decreased (P = 0.05), and ONL thickness was increased (P = 0.04) compared to CNTL. In NPDR subjects, GCLIPL thickness was increased in perifoveal subfields (P< 0.05) and INL intensity was higher in all macular subfields (P = 0.04) compared to CNTL. CONCLUSIONS: Depth and spatially resolved retinal thickness and reflectance measurements are potential biomarkers for assessment and monitoring of DR.

PARS PLANA VITRECTOMY COMBINED WITH CATARACT EXTRACTION: A Comparison of Surgical Outcomes Using Single-Piece and Multipiece Foldable Intraocular Lenses.

PURPOSE: To assess whether complication rates are comparable between phacovitrectomy using multipiece lenses versus single-piece foldable intraocular lenses. METHODS: Single-center, multisurgeon retrospective comparative consecutive interventional case series. Two hundred and seventy-one patients undergoing combined phacovitrectomy performed during a single session at a university-based ophthalmology practice from 2004 to 2013 were identified, of whom 184 met study inclusion criteria; 56.4% patients had diabetes mellitus. RESULTS: There was no difference in the total incidences of postoperative complications between combined surgery using single-piece and multipiece intraocular lenses (P = 0.80) or among individual complications between the 2 groups, including synechiae (2.7 vs. 5.3%; P = 0.61), pupillary capture (0.7 and 2.6%; P = 0.36), and lens subluxation (1.4 and 0%; P > 0.99). There was no difference in the incidences of complications in patients with diabetes mellitus compared with nondiabetic patients undergoing phacovitrectomy (P = 0.13). Complication rates did not differ between single-piece and multipiece lenses with the use of postoperative intravitreal tamponade (P = 0.67). CONCLUSION: Single-piece, acrylic intraocular lenses are associated with a low rate of surgical complications after combined phacovitrectomy and represent an acceptable alternative to multipiece foldable intraocular lenses under the circumstances and using the surgical techniques implemented in this study.

Epidemiological trends in uveal melanoma.

BACKGROUND: There has been a recent evolution in the management of uveal melanoma in regard to prognostic evaluation and treatment modalities. This study aims to evaluate the epidemiological trends of uveal melanoma since 1973 by using the Surveillance, Epidemiology, and End Results (SEER) Registry. METHODS: A total of 7043 uveal melanoma cases from the SEER database were retrospectively analysed, spanning 1973 to 2009. The main outcome measures were disease specific and overall patient survival. RESULTS: The mean patient age at diagnosis was 61.4 years, which has increased over the last 37 years. The mean follow-up interval was 85.9 months. The proportion of tumours demonstrating spindle cell histology has decreased. Spindle cell tumours yielded superior disease-specific survival to epithelioid and mixed tumours. The median age at diagnosis of spindle cell tumours (60 years) was significantly younger than epithelioid tumours (65 years) and mixed tumours (64 years old; p < 0.0001). In a Cox proportional hazards regression analysis, tumour histology, T stage and age at diagnosis were associated with disease-specific survival. The prevalence of cutaneous melanoma was increased in patients with uveal melanoma, but the lifetime prevalence of other primary cancers was not appreciably increased. CONCLUSIONS: The SEER data set demonstrates epidemiological trends in patient age at diagnosis and tumour histology over the last 37 years. Several patient and tumour characteristics are predictors of disease-specific survival. These findings have implications for disease surveillance and prognostic counselling.

Epithelial downgrowth after Ahmed implantation presenting as a peritubular fibrovascular membrane.

This is a case report of a 54-year-old woman with chronic uveitis who developed epithelial downgrowth after an Ahmed valve implantation. The epithelial downgrowth presented in an unusual fashion, as a peritubular fibrovascular membrane. Our case suggests that in patients who have undergone glaucoma drainage implantation with clinical features such as persistent hypotony and atypical inflammatory cells, high clinical suspicion for epithelial downgrowth and careful search for potential fistulas are necessary, even without an obvious wound leak.