Artificial intelligence-based stratification of demographic, ocular surface high-risk factors in progression of keratoconus.

Purpose: The purpose of this study was to identify and analyze the clinical and ocular surface risk factors influencing the progression of keratoconus (KC) using an artificial intelligence (AI) model. Methods: This was a prospective analysis in which 450 KC patients were included. We used the random forest (RF) classifier model from our previous study (which evaluated longitudinal changes in tomographic parameters to predict "progression" and "no progression") to classify these patients. Clinical and ocular surface risk factors were determined through a questionnaire, which included presence of eye rubbing, duration of indoor activity, usage of lubricants and immunomodulator topical medications, duration of computer use, hormonal disturbances, use of hand sanitizers, immunoglobulin E (IgE), and vitamins D and B12 from blood investigations. An AI model was then built to assess whether these risk factors were linked to the future progression versus no progression of KC. The area under the curve (AUC) and other metrics were evaluated. Results: The tomographic AI model classified 322 eyes as progression and 128 eyes as no progression. Also, 76% of the cases that were classified as progression (from tomographic changes) were correctly predicted as progression and 67% of cases that were classified as no progression were predicted as no progression based on clinical risk factors at the first visit. IgE had the highest information gain, followed by presence of systemic allergies, vitamin D, and eye rubbing. The clinical risk factors AI model achieved an AUC of 0.812. Conclusion: This study demonstrated the importance of using AI for risk stratification and profiling of patients based on clinical risk factors, which could impact the progression in KC eyes and help manage them better.

Efficacy of customized corneal crosslinking versus standard corneal crosslinking in patients with progressive keratoconus (C-CROSS study): study protocol for a randomized controlled trial.

BACKGROUND: Keratoconus is a degenerative disorder of the cornea leading to a protrusion and thinning with loss of visual acuity. The only treatment to halt the progression is corneal crosslinking (CXL), which uses riboflavin and UV-A light to stiffen the cornea. Recent ultra-structural examinations show that the disease is regional and does not affect the entire cornea. Treating only the affected zone with CXL could be as good as the standard CXL, that treats the entire cornea. METHODS: We set up a multicentre non-inferiority randomized controlled clinical trial comparing standard CXL (sCXL) and customized CXL (cCXL). Patients between 16 and 45 years old with progressive keratoconus were included. Progression is based on one or more of the following changes within 12 months: 1 dioptre (D) increase in keratometry (Kmax, K1, K2); or 10% decrease of corneal thickness; or 1 D increase in myopia or refractive astigmatism, requiring corneal crosslinking. DISCUSSION: The goal of this study is to evaluate whether the effectiveness of cCXL is non-inferior to sCXL in terms of flattening of the cornea and halting keratoconus progression. Treating only the affected zone could be beneficial for minimalizing the risk of damaging surrounding tissues and faster wound healing. Recent non-randomized studies suggest that a customized crosslinking protocol based on the tomography of the patient's cornea may stop the progression of keratoconus and result in flattening of the cornea. TRIAL REGISTRATION: This study was prospectively registered at ClinicalTrials.gov on August 31st, 2020, the identifier of the study is NCT04532788.

Evaluation of Biomechanical Changes After Accelerated Cross-Linking in Progressive Keratoconus: A Prospective Follow-Up Study.

PURPOSE: The aim of this study was to analyze the biomechanical effect of accelerated corneal cross-linking (9*10) in progressive keratoconus (KC) in comparison to untreated fellow eyes using Scheimpflug-based tonometry (Corvis ST, CVS). METHODS: Forty-three eyes of 43 patients with KC showed progressive KC and were treated using accelerated corneal cross-linking. Twenty-five untreated fellow eyes were used as the control group. All eyes were examined biomechanically (CVS) and tomographically (Pentacam) at baseline, after 1-month, 6-month, and 12-month follow-up. Statistical analysis was performed using a linear mixed model. A logistic regression was performed to attribute the effects of changes in each parameter to treatment status (treated or untreated). RESULTS: Maximum keratometry values decreased statistically significantly at 12 months by -1.1 D (95 confidence interval: -2.0 to -0.1, P = 0.025) compared with baseline. Thinnest corneal thickness decreased significantly after 1 month ( P < 0.001) and recovered to baseline after 12 months ( P = 0.752). In the corneal cross-linking (CXL) group, biomechanical changes were observed by an increased bIOP, a shorter A2 time, and a lower integrated radius after 1 month (all P < 0.05). No biomechanical and tomographical changes were observed in the control group (all P > 0.05). Logistic regression pointed out that treated eyes can be separated from untreated eyes by differences in bIOP, corneal thickness, A1 velocity, integrated radius, and Kc mean at 1, 6, and 12 months. CONCLUSIONS: The alterations in biomechanical parameters indicated a corneal stiffening effect after CXL treatment, which was mostly detectable 1 month after treatment, although corneal thickness was reduced. The logistic regression model showed an adequate separation between CXL-treated and untreated eyes.

Impact of crossplay between ocular aberrations and depth of focus in topo-guided laser-assisted in situ keratomileusis outcomes.

Purpose: To develop a nomogram in cases with mismatch between subjective and Topolyzer cylinder, and based on the magnitude of the mismatch, customize a treatment plan to attain good visual outcomes post-laser-assisted in situ keratomileusis (LASIK) surgery. Methods: The patients were evaluated preoperatively using corneal tomography with Pentacam. Five optimal corneal topography scans were obtained from the Topolyzer Vario were used for planning the LASIK treatment. For the nomogram purpose, the patients were divided into three categories based on the difference between the subjective cylinder and Topolyzer (corneal) cylinder. The first group (group 1) consisted of eyes of patients, where the difference was less than or equal to 0.4 D. The second group (group 2) consisted of eyes, where the difference was more than 0.4 D and the subjective cylinder was lesser than the Topolyzer cylinder. The third group (group 3) included eyes where the difference was more than 0.4 D but the subjective cylinder was greater than the Topolyzer cylinder. LASIK was performed with the WaveLight FS 200 femtosecond laser and WaveLight EX500 excimer laser. Assessment of astigmatism correction for the three groups was done using Aplins vector analysis. For comparison of proportions, Chi-square test was used. A P value less than 0.05 was considered statistically significant. Results: The UDVA was statistically significantly different when compared between groups 1 and 2 (P = 0.02). However, the corrected distance visual acuity (CDVA) was similar among all the three groups (P = 0.1). Group 3 showed an increase of residual cylinder by -0.25 D, which was significant at intermediate and near reading distances (P < 0.05). Group 3 showed significantly higher target-induced astigmatism (TIA) compared to groups 1 and 2 (P = 0.01). The mean surgically induced astigmatism (SIA) was the least in group 2, which was statistically significant (P < 0.01). Conclusion: The outcomes for distance vision using our nomogram postoperatively were excellent, but further refinement for improving the near vision outcomes is required.

A novel combination of corneal confocal microscopy, clinical features and artificial intelligence for evaluation of ocular surface pain.

OBJECTIVES: To analyse various corneal nerve parameters using confocal microscopy along with systemic and orthoptic parameters in patients presenting with ocular surface pain using a random forest artificial intelligence (AI) model. DESIGN: Observational, cross-sectional. METHODS: Two hundred forty eyes of 120 patients with primary symptom of ocular surface pain or discomfort and control group of 60 eyes of 31 patients with no symptoms of ocular pain were analysed. A detailed ocular examination included visual acuity, refraction, slit-lamp and fundus. All eyes underwent laser scanning confocal microscopy (Heidelberg Engineering, Germany) and their nerve parameters were evaluated. The presence or absence of orthoptic issues and connective tissue disorders were included in the AI. The eyes were grouped as those (Group 1) with symptom grade higher than signs, (Group 2) with similar grades of symptoms and signs, (Group3) without symptoms but with signs, (Group 4) without symptoms and signs. The area under curve (AUC), accuracy, recall, precision and F1-score were evaluated. RESULTS: Over all, the AI achieved an AUC of 0.736, accuracy of 86%, F1-score of 85.9%, precision of 85.6% and recall of 86.3%. The accuracy was the highest for Group 2 and least for Group 3 eyes. The top 6 parameters used for classification by the AI were microneuromas, immature and mature dendritic cells, presence of orthoptic issues and nerve fractal dimension parameter. CONCLUSIONS: This study demonstrated that various corneal nerve parameters, presence or absence of systemic and orthoptic issues coupled with AI can be a useful technique to understand and correlate the various clinical and imaging parameters of ocular surface pain.

Correlation of Volume of Macular Edema with Retinal Tomography Features in Diabetic Retinopathy Eyes.

Optical coherence tomography (OCT) enables the detection of macular edema, a significant pathological outcome of diabetic retinopathy (DR). The aim of the study was to correlate edema volume with the severity of diabetic retinopathy and response to treatment with intravitreal injections (compared to baseline). Diabetic retinopathy (DR; n = 181) eyes were imaged with OCT (Heidelberg Engineering, Germany). They were grouped as responders (a decrease in thickness after intravitreal injection of Bevacizumab), non-responders (persistent edema or reduced decrease in thickness), recurrent (recurrence of edema after injection), and treatment naïve (no change in edema at follow-up without any injection). The post-treatment imaging of eyes was included for all groups, except for the treatment naïve group. All eyes underwent a 9 × 6 mm raster scan to measure the edema volume (EV). Central foveal thickness (CFT), central foveal volume (CFV), and total retinal volume (TRV) were obtained from the early treatment diabetic retinopathy study (ETDRS) map. The median EV increased with DR severity, with PDR having the greatest EV (4.01 mm3). This correlated positively with TRV (p < 0.001). Median CFV and CFT were the greatest in severe NPDR. Median EV was the greatest in the recurrent eyes (4.675 mm3) and lowest (1.6 mm3) in the treatment naïve group. Responders and non-responders groups had median values of 3.65 and 3.93 mm3, respectively. This trend was not observed with CFV, CFT, and TRV. A linear regression yielded threshold values of CFV (~0.3 mm3), CFT (~386 µm), and TRV (~9.06 mm3), above which EV may be detected by the current scanner. In this study, EV provided a better distinction between the response groups when compared to retinal tomography parameters. The EV increased with disease severity. Thus, EV can be a more precise parameter to identify subclinical edema and aid in better treatment planning.

Risk Assessment of Aerosol Generation During Vitreoretinal Surgery Using High Speed Imaging Amidst the COVID-19 Pandemic.

Purpose: The purpose of this study was to discuss the propensity of aerosol and droplet generation during vitreoretinal surgery using high speed imaging amidst the coronavirus disease 2019 (COVID-19) pandemic. Methods: In an experimental set up, various steps of vitreoretinal surgery were performed on enucleated goat eyes. The main outcome measures were visualization, quantification of size, and calculation of aerosol spread. Results: During intravitreal injection, insertion of cannulas, lensectomy, and vitrectomy with both 23 and 25-gauge instruments, with either valved or nonvalved cannulas, aerosols were not visualized which was confirmed on imaging. Although there was no aerosol generation during active fluid air exchange (FAE), there was bubbling and aerosol generation at the exit port of the handle during passive FAE. Under higher air pressure, with reused valved and fresh nonvalved cannulas, aerosol generation showed a trajectory 0.4 to 0.67 m with droplet size of 200 microns. Whereas removing cannulas or suturing under active air infusion (35 mm Hg and above) aerosols were noted. Conclusions: Based on the above experiments, we can formulate guidelines for safe vitrectomy during COVID-19. Some recommendations include the use of valved cannulas, avoiding passive FAE or to direct the exit port away from the surgeon and assistant, and to maintain the air pressure less than or equal to 30 mm Hg. Translational Relevance: In the setting of the COVID-19 pandemic, the risk from virus laden aerosols, as determined using an experimental setup, appears to be low for commonly performed vitreoretinal surgical procedures.

Fluid dynamics of droplet generation from corneal tear film during non-contact tonometry in the context of pathogen transmission.

Noninvasive ocular diagnostics demonstrate a propensity for droplet generation and present a potential pathway of distribution for pathogens such as the severe acute respiratory syndrome coronavirus 2. High-speed images of the eye subjected to air puff tonometry (glaucoma detection) reveal three-dimensional, spatiotemporal interaction between the puff and tear film. The interaction finally leads to the rupture and breakup of the tear film culminating into sub-millimeter sized droplet projectiles traveling at speeds of 0.2 m/s. The calculated droplet spread radius ( ∼ 0.5 m) confirms the likelihood of the procedure to generate droplets that may disperse in air as well as splash on instruments, raising the potential of infection. We provide a detailed physical exposition of the entire procedure using high fidelity experiments and theoretical modeling. We conclude that air puff induced corneal deformation and subsequent capillary waves lead to flow instabilities (Rayleigh-Taylor, Rayleigh-Plateau) that lead to tear film ejection, expansion, stretching, and subsequent droplet formation.

Optical coherence tomography angiography (OCTA) of retinal vasculature in patients with post fever retinitis: a qualitative and quantitative analysis.

Post fever retinitis is a heterogenous entity that is seen 2-4 weeks after a systemic febrile illness in an immunocompetent individual. It may occur following bacterial, viruses, or protozoal infection. Optical coherence angiography (OCTA) is a newer non-invasive modality that is an alternative to fundus fluorescein angiography to image the retinal microvasculature. We hereby describe the vascular changes during the acute phase of post fever retinitis on OCTA. Imaging on OCTA was done for all patients with post fever retinitis at presentation with 3 × 3 mm and 8 × 8 mm scans centred on the macula and corresponding enface optical coherence tomography (OCT) scans obtained. A qualitative and quantitative analysis was done for all images. 46 eyes of 33 patients were included in the study. Salient features noted were changes in the superficial (SCP) and deep capillary plexus (DCP) with capillary rarefaction and irregularity of larger vessels in the SCP. The DCP had more capillary rarefaction when compared to the SCP. The foveal avascular zone (FAZ) was altered with an irregular perifoveal network. Our series of post fever retinitis describes the salient vascular features on OCTA. Although the presumed aetiology was different in all our patients, they developed similar changes on OCTA. While OCTA is not useful if there is gross macular oedema, the altered FAZ can be indicative of macular ischemia.

Propensity of aerosol and droplet creation during oculoplastic procedures: A risk assessment with high-speed imaging amidst COVID-19 pandemic.

PURPOSE: The study uses principles of liquid and gas mechanics to verify and quantify the generation of aerosols in oculoplastic procedures, namely surgery using a scalpel, electrosurgical device, and a mechanized drill. METHODS: Surgical techniques were performed ex vivo using the electrosurgical device, scalpel, and mechanized drill on the muscle and bone of commercially available chicken. The liquid and gas dynamics were observed using a high-speed high-resolution Photron SA5 camera (0.125 to 8 ms temporal resolution, 0.016 to 0.054 mm/pixel spatial resolution) and stroboscopic lighting (Veritas 120 E LED Constellation). The analysis was performed using in-house algorithms and ImageJ software. RESULTS: The use of a mechanized drill at 35000 rpm and a 3 mm fluted burr generated aerosol with particle size 50 to 550 microns with a spread of 1.8 m radius. Surgical smoke was generated by an electrosurgical device in both cutting and coagulation modes. Dispersion of the smoke could be controlled significantly by the use of suction, mean smoke spread ratio being 0.065 without suction and 0.002 with use of suction within 2 cm. CONCLUSION: The quantification of the aerosol generation will help surgeons take practical decisions in their surgical techniques in the pandemic era.

Intracorneal Ring Segments Followed by Simultaneous Topography-Guided Removal of Epithelium and Stroma With Accelerated Collagen Cross-Linking For Keratoconus (I-TRESK/CXL).

PURPOSE: The aim of this study was to assess the visual, topographic, and aberrometric outcomes of a novel tissue sparing technique, topography-guided removal of epithelium, and stroma in keratoconus (TRESK) along with accelerated collagen cross-linking (CXL), 1 month after Intacs insertion. DESIGN: Prospective interventional study. METHODS: Fourty-eight eyes (45 patients) with keratoconus underwent femto-assisted Intacs insertion. After 1 month, TRESK and CXL (9 mW/cm2 for 10 minutes) was done. TRESK is a decentered trans-PTK (phototherapeutic keratectomy) with center and area of ablation at the location of the steepest tangential anterior curvature and area of the cone respectively. Total ablation (epithelium plus stroma) was limited to 75 µm. Postoperative measurements were performed 1 month after Intacs, 6 weeks after Intacs followed by TRESK/CXL, and at the final visit 12 months after Intacs followed by TRESK/CXL. RESULTS: For all eyes studied, uncorrected distance visual acuity and corrected distance visual acuity (CDVA) (logMAR) improved from preoperative means of 1.05 ±â€Š0.05 and 0.31 ±â€Š0.03 logMAR to postoperative means of 0.52 ±â€Š0.05 (P < 0.001) and 0.20 ±â€Š0.02 logMAR (P = 0.009), respectively. The mean preoperative sphere, cylinder and mean refractive spherical equivalent decreased from -4.52 ±â€Š0.98 D, -4.81 ±â€Š0.25 D, -6.93 ±â€Š0.99 D to -0.77 ±â€Š0.53 D (P = 0.029), -3.13 ±â€Š0.24 D (P = 0.002), and -2.34 ±â€Š0.53 D (P = 0.021), respectively with a mean keratometric flattening of 5.06D (P < .0001) at the final visit. In total, 2.08% of the eyes lost 1 Snellen line of CDVA. Sixty eight percent and 27% of the eyes gained 2 Snellen lines or more of uncorrected distance visual acuity and CDVA, respectively. CONCLUSIONS: Simultaneous TRESK with CXL done 1 month after Intacs insertion (I-TRESK) in keratoconus eyes provided significant visual gain with refractive and topographic improvement. This novel procedure involving customized PTK before CXL is safe, easy to plan and perform, and provides good outcomes.

Enhanced Vitreous Imaging in Uveitis.

PURPOSE: To study the structural visibility of the posterior vitreous cavity and vitreoretinal interface using Spectral Domain-Optical Coherence Tomography in patients with uveitis using conventional, Enhanced Depth Imaging (EDI), Combined Depth Imaging (CDI), and Enhanced Vitreous Imaging (EVI) techniques. METHODS: It was an observational cross-sectional study of 59 eyes of 33 patients between age group 12-72 years (Median 43) diagnosed as uveitis with posterior segment manifestations underwent OCT using conventional, EDI, CDI, and EVI techniques. The visibility of posterior vitreous was graded in all the techniques. RESULTS: A statistically significant difference was seen in posterior vitreous visibility on comparing all four techniques. EVI showed better visibility of posterior vitreous cavity compared to all other techniques (P < 0.001). CONCLUSIONS: EVI technique provides better structural visibility of posterior vitreous compared to conventional, EDI, and CDI techniques.

Age and myopia associated optical coherence tomography of retina and choroid in pediatric eyes.

PURPOSE: To evaluate the association between retinal and choroidal thickness and volume along with choroidal vessel volume in children using optical coherence tomography (OCT) images. METHODS: 113 normal eyes of children ranging from 5-17 years of age were imaged with a clinical OCT scanner (Optovue Inc., Fremont, USA). The retina, choroid and choroidal vessels were automatically segmented with algorithms. Parameters evaluated were thickness and volume. Location specific analyses of thickness were also performed at a distance of 2.5 mm from foveal center. Multivariate analyses of variance were used to analyze the effect of age and myopia. Manual segmentation of the fovea and subfoveal choroid thickness was also performed to compare with the algorithm segmentation. RESULTS: There was excellent agreement between manual and automatic segmentation (intra-class correlation of 0.95). Within the same eye, total retinal and choroid thickness of nasal and temporal location were significantly lower than the superior and inferior thickness (P < 0.0001). With age (P = 0.026) and myopia (P < 0.001), foveal thickness increased. Choroid volume, vessel volume and temporal choroid thickness increased with increasing myopia (P < 0.05). There was significant positive correlation between choroid volume and retinal volume (r = 0.62, P < 0.0001), choroid volume and vessel volume (r = 0.48, P < 0.0001), and with foveal thickness (r = 0.31, P = 0.009). Choroid vessel volume also showed significant positive correlations with the other metrics (P < 0.05). CONCLUSION: Retinal and choroidal structural features were quantified simultaneously from OCT images. Magnitude of myopia had a greater effect on retino-choroid features than age in children.