Development, comparison, and internal validation of prediction models to determine the visual prognosis of patients with open globe injuries using machine learning approaches.

INTRODUCTION: Open globe injuries (OGI) represent a main preventable reason for blindness and visual impairment, particularly in developing countries. The goal of this study is evaluating key variables affecting the prognosis of open globe injuries and validating internally and comparing different machine learning models to estimate final visual acuity. MATERIALS AND METHODS: We reviewed three hundred patients with open globe injuries receiving treatment at Khatam-Al-Anbia Hospital in Iran from 2020 to 2022. Age, sex, type of trauma, initial VA grade, relative afferent pupillary defect (RAPD), zone of trauma, traumatic cataract, traumatic optic neuropathy (TON), intraocular foreign body (IOFB), retinal detachment (RD), endophthalmitis, and ocular trauma score (OTS) grade were the input features. We calculated univariate and multivariate regression models to assess the association of different features with visual acuity (VA) outcomes. We predicted visual acuity using ten supervised machine learning algorithms including multinomial logistic regression (MLR), support vector machines (SVM), K-nearest neighbors (KNN), naïve bayes (NB), decision tree (DT), random forest (RF), bagging (BG), adaptive boosting (ADA), artificial neural networks (ANN), and extreme gradient boosting (XGB). Accuracy, positive predictive value (PPV), recall, F-score, brier score (BS), Matthew correlation coefficient (MCC), receiver operating characteristic (AUC-ROC), and calibration plot were used to assess how well machine learning algorithms performed in predicting the final VA. RESULTS: The artificial neural network (ANN) model had the best accuracy to predict the final VA. The sensitivity, F1 score, PPV, accuracy, and MCC of the ANN model were 0.81, 0.85, 0.89, 0.93, and 0.81, respectively. In addition, the estimated AUC-ROC and AUR-PRC of the ANN model for OGI patients were 0.96 and 0.91, respectively. The brier score and calibration log-loss for the ANN model was 0.201 and 0.232, respectively. CONCLUSION: As classic and ensemble ML models were compared, results shows that the ANN model was the best. As a result, the framework that has been presented may be regarded as a good substitute for predicting the final VA in OGI patients. Excellent predictive accuracy was shown by the open globe injury model developed in this study, which should be helpful to provide clinical advice to patients and making clinical decisions concerning the management of open globe injuries.

Evaluating the Efficacy and Safety of Aflibercept Biosimilar (P041) Compared with Originator Product in Patients with Neovascular Age-Related Macular Degeneration.

OBJECTIVE: To assess the noninferiority of biosimilar aflibercept (P041, CinnaGen) to the originator aflibercept (AFL, Regeneron) in terms of efficacy, safety, and immunogenicity. DESIGN: This was a phase Ш, 52-week, multicenter, randomized, double-masked, and active control trial involving eyes in a 1:1 ratio. SUBJECTS: Patients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration randomized into the 2 groups of P041 and AFL. METHODS: Patients received an injection of aflibercept every 4 weeks for 3 doses, followed by administration every 8 weeks up to week 48. MAIN OUTCOME MEASURES: The primary outcome was the noninferiority analysis of eyes maintaining vision at week 52. Secondary outcomes included the changes in visual acuity and retinal thickness, safety evaluation, and immunogenicity during the study. RESULTS: In total, 168 eyes of 168 patients were included. At week 52, the proportion of patients maintaining vision was 94.44% in the P041 group compared with 94.52% in the AFL group. The 95% confidence interval (CI) for the difference of maintaining vision from baseline did not exceed the predefined noninferiority margin of 10% (difference, -0.0008; 95% CI, -0.074 to 0.074; P = 0.98). Secondary outcomes indicated similar results in both arms (all P > 0.05). Safety measured outcomes and immunogenicity were similar between the 2 study groups. CONCLUSIONS: Biosimilar aflibercept was noninferior to AFL in eyes with neovascular age-related macular degeneration. Other efficacy and safety findings also indicated the similarity of 2 products. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

In-situ forming biodegradable implants for sustained Fluocinolone acetonide release to the posterior eye: In-vitro and in-vivo investigations in rabbits.

Delivering medication to the posterior segment of the eye presents a significant challenge. Intravitreal injection has emerged as the preferred method for drug delivery to this area. However, current injectable non-biodegradable implants for fluocinolone acetonide (FA) require surgical removal after prolonged drug release, potentially affecting patient compliance. This study aimed to develop an in-situ forming biodegradable implant (ISFBI) optimal formulation containing PLGA504H and PLGA756S (50:50 w/w%) with the additive NMP solvent. The goal was to achieve slow and controlled release of FA over a two-month period with lower burst release, following a single intravitreal injection. Through morphology, rheology, stability and in-vitro release evaluations, the optimal formulation demonstrated low viscosity (0.12-1.25 Pa. s) and sustained release of FA at a rate of 0.36 µg/day from the third day up to two months. Furthermore, histopathology and in-vivo studies were conducted after intravitreal injection of the optimal formulation in rabbits' eye. Pharmacokinetic analysis demonstrated mean residence time (MRT) of 20.02 ± 0.6 days, half-life (t1/2) of 18.80 ± 0.4 days, and clearance (Cl) of 0.29 ± 0.03 ml/h for FA in the vitreous humor, indicating sustained and slow absorption of FA by the targeted retinal tissue from vitrea over the two-month period and eliminating through the anterior section of the eye, as revealed by its presence in the aqueous humor. Additionally, FA exhibited no detection in the blood and no evidence of systemic side effects or damage on the retinal layer and other organs. Based on these findings, it can be concluded that in-situ forming injectable biodegradable PLGA implants can show promise as a long-acting and controlled-release system for intraocular drug delivery.

Evaluation of Macular Neurovasculature and Choroidal Blood Flow Following Inferior Oblique Myectomy Using Optical Coherence Tomography Angiography.

PURPOSE: To evaluate the short-term effects of inferior oblique myectomy on the retinal neurovasculature, choroidal thickness, and choroidal vascularity index at the macula. METHODS: Patients older than 5 years who were candidates for inferior oblique muscle myectomy surgery participated in the study. Patients with any systemic or ocular disease that could affect the macular neurovasculature were not included in the study. After recording demographic data, including age and gender, and conducting a complete ophthalmic examination, macular optical coherence tomography (OCT), enhanced depth imaging OCT, and OCT angiography imaging (AngioVue software (V.2017.1.0.151; Optovue, Inc) were performed before (1 day to 1 week) and in the specific time intervals (1 week, 1 month, and 3 months) after the surgery for all participants. RESULTS: Eighteen patients (13 male and 5 female) who underwent inferior oblique muscle myectomy, with a mean ± standard deviation age of 24.22 ± 18.14 years, were included in this study. The baseline mean ± standard deviation of subfoveal choroidal luminal area and subfoveal total choroidal area were 0.390 ± 0.03 and 0.539 ± 0.04 mm2, respectively. The changing pattern of the subfoveal choroidal vascularity index and subfoveal choroidal luminal area was statistically significant (P = .013 and .035, respectively). CONCLUSIONS: Inferior oblique myectomy can lead to changes in choroid hemodynamics in the short term. However, these changes seem to be temporary. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XX-XX.].

Atypical Central Retinal Artery Occlusion following COVID-19 Infection: A Case Report.

Herein, we report a patient with atypical central retinal artery occlusion (CRAO) following COVID-19 recovery. A 44-year-old male was referred to the emergency room with a history of diplopia and sudden-onset painless visual loss in his left eye. He had a history of 1-week hospitalization for severe COVID-19 infection with pneumonia 3 weeks before, with positive real-time reverse transcription polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a nasopharyngeal sample. His visual acuity in the left eye was light perception which became no light perception later. Relative afferent pupillary defect was positive in the left eye. He had anterior chamber and anterior vitreous cells due to spillover and white cotton-wool-like patches in the left eye. He was diagnosed with atypical CRAO with uveitis-like features. After 3 weeks, he developed neovascular glaucoma and was treated with panretinal photocoagulation. In conclusion, SARS-CoV-2-induced vasculopathy and hypercoagulopathy conditions may be involved in the progression of CRAO in our patient. COVID-19 could be a considerable predisposing factor for CRAO.

Macular retinal and choroidal thickness profile in patients with thyroid-associated orbitopathy compared to healthy individuals: A cross-sectional study.

Background and Aims: To evaluate the macular thickness profile and central subfoveal choroidal thickness in patients with thyroid-associated orbitopathy (TAO) compared to healthy subjects. Methods: We used the convenience sampling method and divided all participants into the patients and control groups. Based on the clinical activity score (CAS) in the first examination, the patient group was divided to two subgroups: the patients with CAS < 3 and the patients with CAS ≥ 3. Complete ophthalmologic examinations and optical coherence tomography imaging were performed for all participants. Results: The mean ± SD of central choroidal thickness was 277 ± 76.58 microns for the control and 326.07 ± 56.574 micron for the patient group which was statistically significant (p = 0.003). We also found that the parafoveal inner thickness is significantly lower in patients compared to healthy subjects (p = 0.02). A comparison of neuro-structural data between the two subgroups of patients showed a significant difference in central choroidal thickness (p = 0.05). Conclusion: This study showed that central choroidal thickness in patients with CAS ≥ 3 compared to those with CAS < 3 and also in the patient group compared to healthy individuals have a significantly increasing trend.

Macular microvasculature in patients with thyroid-associated orbitopathy: a cross-sectional study.

PURPOSE: The aim of this study was to evaluate macular blood flow in patients with thyroid-associated orbitopathy (TAO) as compared to healthy subjects. The inflammatory nature of the disease, as well as the vascular congestion caused by the increase in the volume of orbital soft tissue and extraocular muscles, rationalize the assessment of retinal blood flow changes in these patients. METHODS: This is a cross-sectional study with the convenience sampling method. Macular flow density was assessed using optical coherence tomography angiography (OCTA) and compared between patients with TAO and healthy individuals. We also compared macular flow density in two subgroups of patients based on clinical activity score (CAS). RESULTS: Eighty-five cases, including 30 healthy individuals and 55 patients with TAO, participated. The foveal avascular zone (FAZ) area was significantly larger in the patient group than in the control. Patients with active TAO with CAS 3 or more had significantly larger FAZ areas than those with CAS less than 3 (p = 0.04). CONCLUSION: We showed that the FAZ area is larger in active TAO patients and can be considered a possible candidate feature for monitoring disease activity and thyroid-associated vasculopathy.

Uveitis including Vogt-Koyanagi-Harada syndrome following inactive covid-19 vaccination: a case series.

BACKGROUND: Currently, large populations have been vaccinated against COVID-19. The whole inactivated Sinopharm COVID-19 vaccine has been the main available COVID-19 vaccine in Iran. Ocular inflammatory reactions have been reported following vaccination. The present case reports aim to introduce four cases of uveitis after the Sinopharm vaccine administration. CASE PRESENTATION: Our first reported case is a 38-year-old woman with a positive medical history of inactive ulcerative colitis. Active uveitis had developed following the second dose of the COVID-19 vaccination. The remaining three cases were healthy individuals who developed the first episode of uveitis, after the COVID-19 vaccine administration. Vogt-Koyanagi-Harada syndrome was the final diagnosis in one of the aforementioned cases. All four patients demonstrated favorable responses to corticosteroid treatment. CONCLUSION: These observations are in line with incoming reports from all around the world and raise concerns about the possibility of post-vaccination uveitis development, especially in cases with a previous history of auto-immune systemic diseases or inactive uveitis.

Bilateral anterior ischemic optic neuropathy and choroidal ischemia in a patient with COVID-19 infection.

A 57-year-old male known case of diabetes mellitus presented with gradually bilateral decreased vision accompanied by ocular pain two weeks after diagnosis of SARS-CoV-2 infection. The results of examination and imaging were indicative of bilateral anterior ischemic optic neuropathy (AION) and massive choroidal ischemia, which may be associated with SARS-CoV-2-induced damages, including endothelial damage, hypercoagulable state, and hypoxia.

Incidence rate and clinical characteristics of acute endophthalmitis following 23-gauge pars plana vitrectomy.

PURPOSE: In this study, we evaluated the incidence and clinical characteristics of post-vitrectomy acute endophthalmitis in a tertiary eye center. METHODS: Data were obtained by reviewing the patients' medical records who underwent primary pars plana vitrectomy (PPvitx) from September 2011 to March 2017. We excluded patients who had any ocular surgery in the past 6 months, immunocompromised patients, and patients with a pre-operative diagnosis of endophthalmitis. The primary outcome was the incidence of acute post-pars plana vitrectomy endophthalmitis. RESULTS: Out of 6474 cases who underwent PPvitx, 12 cases of endophthalmitis (incidence rate of 0.18%) were identified. We found two positive cultures for staphylococcus epidermidis and one positive culture for staphylococcus aureus. Underlying causes of primary vitrectomy in patients who got endophthalmitis were diabetic retinopathy (8 cases), rhegmatogenous retinal detachment (2 cases), and the epiretinal membrane (1 case), and non-clearing vitreous hemorrhage secondary to central retinal vein occlusion (1 case). CONCLUSION: In the present study, the rate of post-vitrectomy acute endophthalmitis was higher than in other reported studies.

Acute effects of coffee consumption on the microcirculation of macula and optic nerve head.

Purpose: This study aimed to evaluate the acute changes in retinal vasculature following coffee consumption. Methods: This is an interventional case series. The subjects were 22 healthy young adults. They were asked to rest in a silent room for 15 min; then, their heart rate, blood pressure, and arterial oxygen saturation pressure were measured with a single patient monitoring system. Optical coherence tomography (OCT) and OCT angiography (OCT-A) imaging of the disc and macula were performed for both eyes of the subjects. These measurements were repeated 45 min after drinking a cup of 450 ml of coffee containing a standard dose of 130 mg of caffeine. Macular and optic nerve head neurovasculature changes were assessed. Results: The results of our study did not show a significant change in peripapillary retinal nerve fiber layer thickness and neural structural and vascular parameters of the optic nerve head. Although assessments of macular vasculature showed a significant decrement in superficial (p = 0.01) and deep vessel density (p = 0.05) at parafovea, vessel densities (VDs) at the fovea, and deep capillary plexus at perifovea showed no significant change. Conclusion: Consuming one cup of coffee (150 mg caffeine) statistically changes central foveal thickness and parafoveal blood flow but likely does not have a clinical impact in healthy young adults.

Optic nerve head optical coherence tomography angiography findings in patients with thyroid eye disease: a case-control study.

BACKGROUND: To evaluate changes in the vessel density (VD) of the optic nerve head (ONH) microvasculature in thyroid eye disease (TED) using optical coherence tomography angiography (OCTA). This study aimed to applicate the OCTA as a noninvasive modality in screening TED patients to assess sub-clinical changes. METHODS: In a cross-sectional study, the control group patients were healthy individuals with no ocular abnormalities and were euthyroid. All patients with TED had clinical features of the disease. We divided them into two groups using the clinical activity score (CAS). Patients with CAS scores 0-2 were categorized as group A, and scores three or more as group B. All vessels (AV) and small vessels (SV) VD inside disc and radial peripapillary capillary network were measured using the ONH-OCTA. RESULTS: We evaluated 29 patients with TED and 28 healthy controls. The mean whole image AV VD (mean ± SD: 56.33 ± 2.56, p-value = 0.17) and the mean whole image SV VD (mean ± SD: 49.94 ± 2.56, p-value = 0.16) in the TED group had no statically significant difference compared with the control group (AV mean ± SD: 57.20 ± 20.22, SV mean ± SD: 50.84 ± 2.23). We found a non-significant decrease in AV and SV radial peripapillary capillary VD in the TED group. There was a significant decrease in the mean whole image AV VD (mean ± SD: 54.83 ± 3.07, p-value = 0.005) and the mean whole image SV VD (mean ± SD: 48.60 ± 3.18, p-value = 0.013) in CAS group B compared to group A (AV mean ± SD: 57.45 ± 1.33, SV mean ± SD: 50.95 ± 1.37). CONCLUSION: Our study showed non-significant ONH vascular alterations in patients with TED, including reduced VD of ONH in the radial peripapillary capillary. Patients with higher CAS scores had a more noticeable decrease in ONH microvasculature.

Paracentral Acute Middle Maculopathy and Nonischemic Central Retinal Vein Obstruction in a Young Patient with Protein C Deficiency.

Purpose: To report a case of protein C deficiency with paracentral acute middle maculopathy (PAMM) and nonischemic central retinal vein obstruction (NI-CRVO). Case Report. A previously healthy twenty-one-year-old male was referred with sudden-onset, painless, unilateral paracentral scotomata in the right eye for a week. His uncorrected visual acuity was 20/20 in both eyes. In fundus examination of the right eye, mild venous tortuosity, retinal hemorrhages, and a gray-white opacity in the papillomacular bundle were observed. In the macular spectral-domain optical coherence tomography images, a hyperreflective band was noticed at the level of the inner nuclear layer, indicating PAMM. Fundus appearance and fluorescein angiography findings indicated NI-CRVO diagnosis made. The systemic and laboratory evaluations disclosed a protein C deficiency. Conclusion: In this report, in a healthy young male, combined PAMM and NI-CRVO showed to be the cause of blurred vision in the setting of protein C deficiency.

Spectral-domain optical coherence tomography assessment of retinal and choroidal changes in patients with coronavirus disease 2019: a case-control study.

OBJECTIVES: This study aimed to evaluate the retinal and choroidal changes in the macular region of patients with Coronavirus Disease 2019 (COVID-19) using structural spectral-domain optical coherence tomography (SD-OCT) analysis. METHODS: This cross-sectional observational case-control study included patients recovered from COVID-19. The COVID-19 in all participants was confirmed using the reverse transcription-polymerase chain reaction (RT-PCR) technique. The participants had mild to moderate degree of disease without a history of hospitalization, steroid usage, or blood saturation below 92%. Macular SD-OCT was performed at least two weeks and up to one month after recovery from systemic COVID-19. Quantitative and qualitative changes detected by macular SD-OCT imaging were evaluated in COVID-19 recovered patients and compared with the results of age-matched normal controls. RESULTS: Participants in this study included 30 cases (60 eyes) and 60 healthy controls (120 eyes). In total, 17 (28.3%) eyes in patient group showed at least one abnormal finding indicated by macular SD-OCT imaging included hyperreflective lesions in different retinal layers. In addition, dilated choroidal vessels and retinal pigment epitheliopathy were evident in 41 (68.3.6%) and 4 (6.6%) eyes in patient group, respectively, and their OCT findings resembled those with pachychoroid spectrum. No statistically significant differences were observed in retinal layers or retinal volume between the two groups. The mean ± SD subfoveal choroidal thickness (SFCT) was determined at 380.3 ± 12.40 µm, which was significantly thicker than that in control group (310.7 ± 57.5 µm) (P < 0.001). CONCLUSION: Regarding retinal thickness, no significant change was observed in different retina layers of patients with COVID-19; however, there were striking qualitative changes, such as hyperreflective lesions in different retinal layers. The evaluation of choroidal structure and thickness demonstrated remarkable abnormal pachyvessels and significant thickening of the SFCT but the clinical significance of these findings is unknown.

Gas Expansion Three Days after Pars Plana Vitrectomy with Sulfur Hexafluoride 20% Tamponade following Carbon Monoxide Toxicity and Oxygen Therapy.

Purpose: To report an unusual case of gas expansion following oxygen therapy in a patient with sulfur hexafluoride (SF6) 20% tamponade after pars plana vitrectomy. Case Report. A 40-year-old man came to the clinic with severe ocular pain and redness and also vision decrease in his left eye three days after uncomplicated 23-gauge pars plana vitrectomy, internal limiting membrane peeling combined with phacoemulsification, and using 20% SF6 injection as a tamponade agent due to significant cataract and a full-thickness macular hole. In ophthalmic examinations of his left eye, high intraocular pressure (approximately 70 mmHg), a flat anterior chamber, and a gas-filled vitreous cavity were found. The patient had been hospitalized the day before due to carbon monoxide poisoning and had undergone oxygen therapy with a pure 100% mask for three hours. Conclusion: It seems that oxygen therapy or carbon monoxide poisoning increases the volume of gas in the patient's vitreous cavity and the nonexpansile percentage of SF6 expands.

Longitudinal Alterations of Retinal and Choroidal Structure in Patients Recovered from COVID-19.

Objective: To evaluate the midterm longitudinal changes in chorioretinal structures in patients with coronavirus disease 2019 (COVID-19). Methods: Thirty-four eyes of 17 COVID-19 patients were enrolled. The patients underwent retinal and choroidal imaging upon the recovery (baseline) after 1 and 3 months. Retinal measurements in fovea, parafovea, and perifovea were recorded. To calculate choroidal vascularity index (CVI), luminal and total choroidal areas were measured using Sonada's method. Choroidal thickness was measured at the subfovea 500 microns temporal and nasal to the fovea. Results: Mean CVI was 0.64 ± 0.04 at baseline that significantly increased to 0.67 ± 0.05 (P = 0.012) after 1 month and again significantly decreased to 0.63 ± 0.05 after 3 months (P < 0.001). While the stromal component showed a significant decrease between the baseline and first-month values (1.16 ± 0.29 to 1.01 ± 0.27, P = 0.03), the luminal area mostly changed between months 1 and 3 (2.03 ± 0.28 to 1.91 ± 0.23, P = 0.045). The average of subfoveal choroidal thickness and retinal thickness remained unchanged. Conclusion: CVI is increased in patients with COVID-19 1 month after recovery from COVID-19 and returns to baseline values after 3 months. Regarding the reversible nature of changes, there might be a prominent role in inflammation.

Peripapillary Nerve Fiber Layer Thickness and Optic Nerve Head Parameters in Patients Recovered from COVID-19: A Longitudinal Study.

Purpose: To quantify the longitudinal changes of the optic nerve head (ONH) parameters and peripapillary retinal nerve fiber layer (pRNFL) thickness in patients recovered from coronavirus disease 2019 (COVID-19) using spectral-domain optical coherence tomography (OCT) analysis. Materials and Methods: In an observational longitudinal study, in patients recovered from COVID-19, ONH OCT images were recorded at least two weeks after recovery from the systemic disease as the baseline and after one and three-month follow-up. Ganglion cell complex (GCC) analysis, ONH parameters, and pRNFL thickness changes were measured. Results: A total of 36 eyes from 18 recovered COVID-19 patients including eleven (61.2%) females were studied. The average age was 35.5 ± 7.5 years. The pRNFL thickness in the nasal lower sector significantly decreased from 77 ± 18 µm in the first post-COVID-19 month to 74 ± 10 µm in the third month (P=0.8). The average, superior, and inferior pRNFL thickness remained unchanged. The average cup volume significantly decreased from 0.27 ± 0.15 mm3 at baseline to 0.19 ± 0.15 mm3 in the third post-COVID-19 visit (P=0.028). In terms of ONH morphologies including rim, disc and cup to disc area, and the vertical and horizontal ratio, the changes were not significant over the 3-month study period. Focal loss volume and global loss volume values were not changed significantly. Conclusion: Localized defect in the nasal lower sector of pRNFL is observed in 3-month post-recovery from COVID-19. Larger studies with longer follow-ups are required to reveal the exact changes in ONH parameters.

Central Retinal Artery Occlusion after Rhinoplasty Surgery: A Case Report and Literature Review.

Aim: This study was aimed at reporting a case of central retinal artery occlusion (CRAO) after rhinoplasty. Case Report. Unilateral blindness occurred in a 22-year-old woman after rhinoplasty with a history of transient visual loss due to migraine aura and vasospasm. The physical examination of the patient revealed a visual acuity of no light perception in the right eye, a 4+ relative afferent pupillary defect, disc swelling, cherry-red spot in the macula, and ischemic retina in the right eye. Based on the diagnosis of CRAO, the patient underwent anterior chamber paracentesis (AC tap) along with treatment with mannitol and intravenous hydrocortisone. Visual acuity improved to 1/10 after a two-month follow-up. Conclusion: Taking history is very important in rhinoplasty surgery, and vasoconstrictors should be limited in the patients with a suspected history of vasospasm.