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Cataracts are a significant cause of vision loss. Modern treatment of cataracts involve surgical fragmentation, removal, and replacement of the clouded intraocular lens. Femtosecond laser-assisted pretreatment is a recent advancement that is thought to enhance the precision, efficiency, and safety of cataract surgery. In this study, Cumulative Dissipated Energy (CDE) and intraoperative time in cataract surgeries with and without femtosecond laser pretreatment were observed. 700 eyes in 541 patient charts over a 38-day period were included in this retrospective analysis. We conclude that femtosecond laser pretreatment significantly reduces average effective phacoemulsification time (EPT) by 12% and average intraoperative time by 7% as compared to non-femtosecond laser assisted (conventional) cataract surgery, supporting current data on its efficacy.

AMA Research Challenge 2024 

A Retrospective Analysis of Cumulative Dissipated Energy during Phacoemulsification and Operative Time in Cataract Surgery with and without Femtosecond Laser-Assistance

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Background: Type 2 diabetes mellitus (T2DM) remains one of the greatest threats to vision globally. HbA1c is the gold standard biomarker of blood glucose control, but recent studies have begun to explore the role of Glycemic variability (GV) as a complementary metric capable of stratifying patients’ risk of complications independent of HbA1c. Studies have linked greater GV to reduced retinal microvasculature density in type 1 diabetes mellitus (T1DM), potentially a pathophysiological result of increased GV leading to blood vessel damage. However, no studies have examined the effects of GV on the retinal microvasculature in T2DM. Optical coherence tomography angiography (OCTA) has gained acceptance in Ophthalmology to reproducibly quantify the retinal microvasculature. Here, we sought to correlate quantitative retinal OCTA metrics to GV. 
Methods: Cohort study of adult patients with T2DM. We used the publicly available AI READI dataset, which as of July 2024 includes 204 T2DM patients across three data collection sites and contains clinical characteristics, retinal OCTA imaging (Maestro2, Topcon, Tokyo, Japan), and continuous glucose monitoring (CGM; Dexcom G6, Dexcom, San Diego, USA), among other data. OCTA metrics (vessel area density (VAD) and vessel length density (VLD)) were calculated for the superficial (SCP) and deep (DCP) capillary plexuses of each eye of each patient, and patients with VAD or VLD less than 10% or 10mm^-1, respectively, were excluded for low image quality. The coefficient of variation (CoV) of CGM-measured plasma blood glucose recorded every 5 minutes over 10 days was calculated. Patients with a CoV greater than 0.15 for a particular metric were classified as high variation for that metric, and the remainder as low variation. Difference in mean values between high variation and low variation groups were examined for each OCTA metric (unpaired t-tests). Pearson correlation coefficients were calculated for each calculated OCTA metric and the CoV of CGM-measured blood glucose. 
Results: 198 patients were identified with available imaging. Of these 24 were excluded for poor image quality. A statistically significant difference in VAD between high and low-variation patients was identified, with those with higher variability having lower VAD (p<0.05).
Conclusion: This study extends prior results finding a correlation between higher blood glucose variability and lower retinal microvascular density from T1DM to T2DM. Blood glucose variability may play a significant role in the pathophysiology of microvascular disease in diabetes.

Analysis of Retinal Vascular Changes in Type 2 Diabetes Mellitus Patients Using the AI READI Database

Background: Exudative age-related macular degeneration (eAMD) is a retinal disorder that may result in rapid deterioration of central vision. Tests leveraging artificial intelligence (AI) hold the promise of automatically identifying and categorizing pathological features, enabling the timely diagnosis and treatment of eAMD. This Cochrane systematic review and meta-analysis aim to determine the diagnostic accuracy of AI as a triaging tool for eAMD.

Methods: We searched CENTRAL, MEDLINE, Embase, three clinical trial registries, and DANS for the grey literature up to April 2024. We included studies that compared the test performance of algorithms with that of human readers in detecting eAMD on retinal images. Review authors worked in pairs to independently extract data and assess study quality using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool with revised signaling questions. Assuming a common positivity threshold applied by the included studies, we chose random effects bivariate logistic models to estimate summary
sensitivity and specificity as the primary performance metrics.

Results: We identified 36 eligible studies that reported 40 sets of algorithm performance data, encompassing over 16,000 participants and 62,000 images. We included 28 studies (78%) reporting 31 algorithms with usable performance data in the meta-analysis. The included algorithms used retinal image types as input, such as optical coherence tomography images (N=15), fundus images (N=6), and multi-modal imaging (N=7). The predominant core method used was deep neural networks. Only three of the included 40 algorithms were externally validated; the summary sensitivity and specificity were 0.94 (95% CI 0.90 to 0.97) and 0.99 (95% CI 0.76 to 1.00), respectively, when compared to human graders. All three studies had high risk of bias mainly due to potential selection bias from either
a two-gate design or the inappropriate exclusion of potentially eligible retinal images. Twenty-eight algorithms were reportedly either internally validated or tested on a development set. The pooled sensitivity and specificity were 0.93 (95% CI 0.89 to 0.96) and 0.96 (95% CI 0.94 to 0.98), respectively, when compared to human graders. We did not identify significant sources of heterogeneity
among these 28 algorithms.

Conclusion: Low to very low certainty evidence suggests that an algorithm-based test may correctly identify most individuals with eAMD without increasing unnecessary referrals (false positives) in either the primary or the specialty care settings. Limited quality and quantity of externally validated algorithms highlight the need for high-certainty evidence, which will require a standardized definition for the eAMD on different imaging modalities and external validation of the algorithm to assess generalizability.

Artificial intelligence for diagnosing exudative age-related macular degeneration: findings from a Cochrane Diagnostic Test Accuracy Review

Background
The corneal dystrophies are a group of inherited disorders that are typically bilateral, symmetric, and slowly progressive, unaffected by environmental or systemic factors. Four types of corneal endothelial dystrophies, primarily affecting corneal endothelial cells, have been described. Here, we present a novel corneal endothelial dystrophy characterized by peripheral posterior corneal macular opacities and endothelial dysfunction without stromal opacity. Symptomatic individuals develop corneal edema, with successful restoration of vision achieved through endothelial keratoplasty (EK).

Methods
Thirty-five individuals from seven families, including 13 affected individuals exhibiting peripheral posterior corneal macular opacities, endothelial guttae and corneal edema, and 22 unaffected family members were included in this retrospective case series. Whole-exome sequencing was performed in three families and Sanger sequencing of CHST6 was performed in all individuals. Histological examination of Descemet membrane (DM) excised at the time of EK was performed for three probands. Serum keratan sulfate (KS) levels were measured in members of six families. Functional analysis of identified mutations was performed using CHST6 promoter containing CHST6 expression vector in human keratocytes (HK) and corneal endothelial cells (HCEnC).

Results
None of the affected individuals demonstrated a single corneal stromal deposit, either on slit lamp exam or on anterior segment OCT imaging, excluding the diagnosis of Macular Corneal Dystrophy. Five affected individuals from four families underwent EK, with resolution of the corneal edema. CHST6 sequencing revealed a non-coding promoter mutation (c.-690G>C) in all families, either in homozygous state in five affected individuals from three families or in a compound heterozygous state with a coding mutation (p.R211Q, p.Y268C or p.P280L) in seven affected individuals from the other four families. In silico analysis predicted c.-690G>C to be a regulatory variant, located at the RNA polymerase II binding site. Functional analysis demonstrated that c.-690G>C leads to increased KS sulfation in HCEnC with no change of KS sulfation in HK, while coding mutations p.P280L and p.Y268C resulted in decreased KS sulfation in HK and no change of KS sulfation in HCEnC. DM staining revealed elevated levels of sulfated and non-sulfated KS in DM and endothelium in affected probands. Minimum changes in serum sulfated KS levels were observed in affected individuals.

Conclusion
A novel corneal endothelial dystrophy characterized by peripheral posterior corneal macular opacities and endothelial dysfunction without stromal opacities is associated with promoter mutation c.-690G>C in CHST6 gene. We suggest the name Peripheral Macular Endothelial Dystrophy (PMED) to describe this dystrophy that can be and should be managed with EK.


Characterization of a Novel Corneal Dystrophy - Peripheral Macular Endothelial Dystrophy

Background 
Endophthalmitis is a serious ophthalmic inflammatory pathology that can result in blindness. Intravitreal (IVT) injections, commonly used treatment vectors for various retinal diseases, have been associated with the risk of developing endophthalmitis. This study aims to compare the incidence of endophthalmitis following IVT dexamethasone (Ozurdex) and anti-VEGF injections administered by several vitreoretinal specialists in outpatient settings. 

Methods 
We retrospectively reviewed IVT dexamethasone and anti-VEGF injections conducted by a network of vitreoretinal specialists in outpatient settings between January 2019 and January 2024. Data was collected on the incidence of endophthalmitis within two weeks following ocular injections. The total sample size included 330,572 cases: 318,618 anti-VEGF injections and 11,954 IVT dexamethasone injections. Statistical analysis was performed to compare the observed and expected frequencies of endophthalmitis for each treatment group, and the significance was determined using a p-value threshold. 

Results 
The incidence of endophthalmitis following Ozurdex injection was found to be higher compared to anti-VEGF injections. Specifically, 15 cases of endophthalmitis were reported out of 11,954 IVT dexamethasone injections, resulting in an incidence rate of 0.109%. In contrast, 106 cases of endophthalmitis were reported out of 318,618 anti-VEGF injections, yielding an incidence rate of 0.033%. The observed frequency of endophthalmitis for IVT dexamethasone was significantly higher than the expected frequency (0.125% vs. 0.037%), whereas the observed frequency for anti-VEGF injections was lower than the expected frequency (0.033% vs. 0.037%). The difference was statistically significant, P < .0001, indicating that IVT dexamethasone is more likely than anti-VEGF to cause endophthalmitis. 

Conclusion 
The findings of this study suggest that patients receiving IVT dexamethasone injections are at a higher risk of developing endophthalmitis compared to those receiving anti-VEGF injections. This significant difference in incidence rates highlights the need for clinicians to carefully consider the risks and benefits when choosing between these treatment options. Further research is warranted to explore the underlying factors contributing to the increased risk associated with IVT dexamethasone and to develop strategies for minimizing this risk.

Comparative Incidence of Endophthalmitis After Intravitreal Dexamethasone Versus Anti-VEGF Injections: A Retrospective Study

Background: Patients undergoing corneal transplantation are at a higher risk of graft failure with concurrent glaucoma. Despite advances in corneal transplant techniques requiring less steroid use, the risk of vision loss from glaucoma persists. Rho Kinase Inhibitors (RKIs) are a newer class of glaucoma drops that reduce intraocular pressure (IOP); however, their corneal effects are lesser known. Some reports suggest a role in corneal endothelial cell survival, while others report a reversible, reticular edema in cornea transplant patients started on RKIs. These contradictory effects make it difficult to assess the exact scenario in which RKIs help or harm the cornea. Specialists must balance the risk of vision loss from glaucoma with the potential toxicity of glaucoma therapies. The literature mostly consists of case series. This retrospective analysis aims to understand how this recently emerged glaucoma medication impacts corneal grafts.
Methods: A retrospective chart review was conducted on adult patients with corneal transplants treated with topical RKIs (netarsudil 0.02%) between 2018 and 2022 at a tertiary care center. Inclusion criteria consisted of glaucoma diagnosis, any type of corneal transplant, and at least one follow-up visit post-RKI initiation. Data collected included patient demographics, ocular history, RKI use, and outcomes related to graft clarity and glaucoma management.
Results: Thirty patients (mean age 64.2 years) were included. The mean number of previous ocular surgeries was 3.6, and the mean logMAR vision was 0.51. The average number of grafts prior to RKI was 1.83. At baseline, 86.67% of patients were on topical carbonic anhydrase inhibitors, and the mean IOP was 26.6 mmHg. Post-RKI, 66.66% of grafts remained clear, while 33.33% developed corneal edema. Univariate analysis identified the number of previous grafts as a significant predictor of graft failure (p=0.05). Other variables, including RKI duration, glaucoma tube shunts, and CAI use, were not significantly associated with graft failure. Furthermore, 46.7% of patients required additional glaucoma surgeries, and 20% required repeat transplants.
Conclusions: Duration of RKI use did not significantly affect graft survival, though a correlation with the number of prior grafts was noted. The confounding variables and absence of a control group limit the ability to draw isolated conclusions. RKI's elusive effects on the cornea warrant further study as specialists balance mitigating glaucoma and preserving graft clarity. Further studies with larger sample sizes and control groups are necessary to better understand the role of RKIs in patients with corneal transplants and glaucoma.

Effects of Rho Kinase Inhibitors on Corneal Transplant Survival


Background
Ophthalmic image quality is impacted by ocular pathology, decreasing accuracy of artificial intelligence (AI) algorithms classifying these images. This study uses AI to improve image quality on color fundus photos (CFPs) to determine if this will restore an AI algorithm’s accuracy in identifying diabetic retinopathy (DR) despite simulated cataracts (SCs).
Methods
A convolutional neural network (CNN) was trained to classify CFPs as either DR or non-DR. Cataracts were simulated by applying Gaussian blur, and the CNN was used to classify these images. A Very Deep Super-Resolution (VDSR) AI was used to enhance the images with simulated cataracts. The CNN then classified these images.
Results
The CNN was able to classify the dataset without any SC with an accuracy of 93%. This accuracy decreased to 78% with SC, but improved back to 85% after images were enhanced using the VDSR.
Conclusion
This study shows that despite AI accuracy decreasing with noise from SC, it can be improved partially using AI-based image enhancement.


Image Resolution Enhancement for Improving an Artificial Intelligence Algorithm’s Accuracy in Detecting Diabetic Retinopathy through Simulated Cataract

Background:
Stent-based MIGS (sb-MIGS) is a revolutionary technology that allows patients to receive sight-saving procedures in a safer and less invasive way. The utilization of sb-MIGS nationally has yet to be explored. Epic Cosmos is a dataset made up of 260-million patients who receive care at a healthcare institution that uses Epic as their electronic health record system. While Sb-MIGS has become popular over the last 10 years, there has been limited published data focused on demographic variations, making our study the first to investigate this topic. 

Method:
The proportion of patients with a diagnosis of mild or moderate primary open-angle glaucoma (mm-POAG), ICD-10 code H40.11X, was compared to the proportion of patients who underwent sb-MIGS, CPT code 0191T denoting iStent or Hydrus implantation, between 1/2014 - 12/2023.

Results:
19149 patients received sb-MIGS out of 361830 mm-POAG patients. Most mm-POAG patients resided in urban areas (90.3% urban vs 6.5% rural; p<0.01). Most sb-MIGS were performed in urban areas (86.4% vs 9.7%; p<0.01). These splits are somewhat different from the urban/rural population split (80/20) per the 2020 US census. A higher proportion of rural patients underwent sb-MIGS relative to mm-POAG rates (~5/100 rural patients vs ~3/100 urban patients; p<0.01), which coincided with an odds ratio of 26.0. Rural non-Hispanic whites (NHW) (90.9% sb-MIGS vs 90% mm-POAG; p=0.34) and minorities, composed of Black-Americans, American-Indian and Hispanic patients, (9.1% vs 9.2%; p=0.88) received sb-MIGS at rates similar to mm-POAG diagnoses rates. Urban NHWs received sb-MIGS at rates significantly higher than mm-POAG diagnosis rates (73.8% vs 63.4%; p<0.01). Urban minorities received sb-MIGS at considerably lower rates versus mm-POAG diagnosis rates (10.9% vs 37.6%; p<0.01). The Epic customer profile limits this study.

Conclusions:
Our findings suggest that mm-POAG diagnoses and sb-MIGS rates are significantly higher in urban areas, where racial and ethnic barriers to sb-MIGS appear to be exacerbated. While geographic barriers may limit rural communities from getting access to eye care, ethnic and racial barriers may not be as limiting.

Insights from a Nationwide Electronic Health Record Cohort on Disparities in Microinvasive Glaucoma Surgery Utilization

Background
Amidst the growing concern over methamphetamine's ophthalmic sequelae, our study focuses on methamphetamine associated keratitis-induced corneal perforation, a significant but underreported complication of methamphetamine use. Three primary mechanisms have been suspected as the link between methamphetamine use and corneal ulcer formation. Firstly, methamphetamine promotes vasoconstriction which in turn leads to corneal stromal neovascularization. Additionally, methamphetamine can cause neurotrophic keratitis which elevates patients’ pain threshold, potentially delaying care. Methamphetamine users also experience hyper-fixation on foreign body sensations which may result in or worsen epithelial defects due to continued physical irritation of the eye. This retrospective chart review aims to illuminate the correlation between methamphetamine use and the development of corneal ulcer perforation treated with therapeutic penetrating keratoplasty (PKP).
Methods
We evaluated 8 patients with a documented history of methamphetamine use who developed corneal ulcers which perforated and subsequently underwent PKP at Loma Linda University Health. The study assessed post-operative outcomes, including best-corrected visual acuity (BCVA), complications, graft survival, and follow-up duration. Furthermore, concomitant drug use and associated microbial infections were also examined.
Results
Our findings underscore the critical impact of methamphetamine use on ocular health, specifically highlighting risk of keratitis leading to corneal perforations. Post-operative outcomes reveal no significant BCVA improvement (p = 0.8323) and poor graft survival rates with an average graft survival time of less than one year. Additionally, the majority of patients had a challenging clinical course with 71.4% of patients demonstrating inconsistent follow-up and 66.7% of patients with at least 6-months of follow-up data experiencing graft failure within one year of their PKP. More than 50% of patients presented with a significant post-operative complication, including corneal edema, epithelial defects, and corneal neovascularization.
Conclusion
Methamphetamine-induced keratitis presents unique clinical challenges, including a risk for corneal perforation and subsequent need for a therapeutic PKP. Our study highlights the importance of recognizing methamphetamine use as a significant risk factor for severe ocular complications and advocating for early detection and multidisciplinary management to optimize outcomes. The findings call for increased awareness and research into targeted interventions that can reduce the adverse ophthalmic effects of methamphetamine abuse.


Methamphetamine Associated Corneal Ulcer Perforation: Poor Post-Operative Outcomes with Penetrating Keratoplasty

Optimizing Ophthalmology Education via ChatBot-Generated Materials: Readability Analysis of AI-generated Patient Education Materials and North American Neuro-Ophthalmology Society (NANOS) Patient Brochures

Background:
It is crucial that patients are offered concise patient education materials (PEMs) to facilitate an enhanced understanding of diagnoses and treatment options. As the average American reads at an 8th grade reading level, the AMA suggests that PEMs be written at a 6th grade level. Despite significant efforts made by NANOS to provide easily accessible webpages for different diagnoses, treatments, and surgeries, the readability of such materials exceeds these recommended guidelines. AI chatbots such as Chat-GPT and Google’s Bard can generate sophisticated responses to free-text input and modifying responses to user feedback. When prompted appropriately, such technology offers promising application to fill the need for more comprehensible ophthalmological PEMs. As such, the aim of this study is to compare the readability of North American Neuro-Ophthalmology Society (NANOS) patient brochures to that of PEMs generated by the AI-chat bots ChatGPT 3.5 and Google Bard.

Methods:
PEMs on 13 common neuro-ophthalmology topics were generated by ChatGPT 3.5 and Google Bard, with and without a 6th grade reading level prompt. The PEMs were analyzed using seven readability metrics: Flesch Reading Ease score, Gunning Fog Index, Flesch-Kincaid Grade Level, Coleman–Liau Index, SMOG Index Score, Automated Readability Index, and Linsear Write Readability Score. Each AI-generated PEM was compared with the equivalent NANOS PEM. 

Results:
When comparing ChatGPT generated PEMs to NANOS brochures, unprompted ChatGPT PEMs consistently had lower readability scores (Flesch-Reading Ease Score NANOS 49.5 ± 3.3; ChatGPT 43.8 ± 8.8, p = 0.04) and higher grade level-equivalent readability scores (SMOG index NANOS 9.7 ± 0.5; ChatGPT 10.4 ± 1.0, p = 0.04), indicating that this material may be the most difficult to comprehend in its unprompted form. On the other hand, Bard generated PEMs that corresponded to a lower grade level compared to NANOS brochures (Linsear-Write Formula NANOS 12.1 ± 1.5; Bard 10.6 ± 2.2), though this difference was non-significant. However, when prompted to produce PEMs at a 6th grade reading level, both ChatGPT and Bard possessed far superior readability scores across all readability metrics compared to NANOS texts. The grade-level equivalent averaged around 8 for both ChatGPT and Google Bard, whereas NANOS brochures corresponded to an 11th grade level.

Conclusion:
This study offers compelling evidence that, when prompted appropriately, AI chat bots can generate comprehensible PEMs for patients on a variety of neuro-ophthalmology topics. Use of this technology in a clinical setting may offer patients with succinct and readable information on complex topics and can guide patient-oriented decision making. Furthermore, use of AI chat bots in this manner may be clinically beneficial in satellite centers where there is a scarcity of neuro-ophthalmologists by assisting triage of patients for neuro-ophthalmology referrals.

Optimizing Ophthalmology Patient Education via ChatBot-Generated Materials: Readability Analysis of AI-generated Patient Education Materials and the North American Neuro-Ophthalmology Society Patient Brochures

Purpose: The role of face-down posturing following rhegmatogenous retinal detachment (RRD) repair remains a consistent management component; however, there is no direct evidence to allow firm conclusions as to what role face-down positioning plays following RRD repair with modern micro-incisional vitrectomy surgery (MIVS) platforms. We evaluated the anatomic and visual outcomes of primary vitrectomy for RRD repair, employing no amount of post-operative prone positioning (POPP) to clarify the role of face-down posturing for RRD re-attachment.

Methods: Retrospective consecutive interventional case series of 116 eyes in 116 patients undergoing primary vitrectomy for RRD repair. Surgical outcomes, single surgery anatomic success (SSAS), and post-operative best-corrected visual acuity (BCVA) were investigated. The primary objective is to study the anatomic and visual outcomes of vitrectomy RRD re-attachment employing no POPP.

Results: SSAS was achieved in 112 (96.5%) of 116 eyes; SSAS was 100% in phakic patients (n=56) and 93% in pseudophakic patients (n=60), with both groups experiencing a mean improvement in BCVA. 

Conclusions: Primary vitrectomy with no POPP is a successful surgical intervention for RRD repair. Our current anatomical closure rate is one of the highest reported in the literature and involved a large number of macula-off RRDs, with minimal complications and significant improvement in BCVA, primarily using 14% C3F8 for gas tamponade.

Outcomes of Primary Vitrectomy for Rhegmatogenous Retinal Detachment: Interventional Retrospective Consecutive Case Series of 116 Patients with no Post-operative Prone Positioning

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A Retrospective Analysis of Cumulative Dissipated Energy during Phacoemulsification and Operative Time in Cataract Surgery with and without Femtosecond Laser-Assistance

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Analysis of Retinal Vascular Changes in Type 2 Diabetes Mellitus Patients Using the AI READI Database

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