OBJECTIVE: To determine whether there is a significant association between inflammatory cytokines in the tear fluid and the severity of Retinopathy of Prematurity (ROP).
METHODS: Retrospective cohort study.
METHODS: The cytokine levels in tear fluids were determined in 34 eyes with ROP and 18 eyes without ROP. There were 15 eyes with severe ROP requiring treatment and 19 eyes with mild ROP not requiring treatment. For severe ROP eyes, tear fluids were collected before treatment.
RESULTS: Significantly higher levels of CCL2 and vascular endothelial growth factor (VEGF) were detected in eyes with severe ROP compared to eyes with mild ROP and no ROP. When assessed for cytokine levels that discriminate each disease group, CCL2 showed a significant odds ratio of 1.76 for severity change (/quintile, P = 0.032, after adjusting for birth weight). Correlation analysis showed that birth weight correlated with IL-1α levels, and decreased weight gain increased IFN-γ levels. We next determined tear fluid cytokines which discriminate severe ROP using receiver operating characteristics\' analysis. We found that combination of higher CCL2 levels, higher VEGF levels, and lower IFN-γ levels in the tear fluid had a stronger predictive value for severe ROP (area under curve, 0.85).
CONCLUSIONS: The levels of CCL2, VEGF, and IFN-γ in tear fluid may serve as useful biomarkers for assessing the severity of ROP.

UNASSIGNED: This retrospective cohort study presents a group of patients who underwent laser therapy for retinopathy of prematurity and presented with delayed anterior segment complications.
UNASSIGNED: The charts of infants treated with laser photocoagulation for retinopathy of prematurity at our institution between 1988 and 2020 were reviewed. The data extracted included demographics, treatment and clinical examination findings, and those on visual acuity, surgical procedures, and cycloplegic refraction. The inclusion criteria were documented anterior segment changes during the follow-up period. The exclusion criteria were any prior intraocular surgery or inflammation before signs of anterior segment complications developed. The exposure was laser photocoagulation for retinopathy of prematurity and the main outcomes were anterior segment complications, visual acuity, and cycloplegic refraction.
UNASSIGNED: A total of 183 charts were reviewed. Sixteen eyes of nine patients (4.4%) met the inclusion criteria. The mean follow-up period after laser treatment was 15.9 years (range 10 years-26 years). The mean gestational age at birth was 24.6 weeks (range 23 weeks-27 weeks), and the mean age at first clinical documentation of anterior segment complications was 8.7 years (range 1 years-25 years). The complications included cataract (n = five patients/eight eyes) and glaucoma (n = three patients/five eyes), with the most frequent complication being band keratopathy (n = nine patients/15 eyes). A total of five out of 16 eyes underwent surgical procedures due to anterior segment complications. After treatment, visual acuity improved back to its baseline value in four out of five of the treated eyes, and improved, but not to its baseline value, in one out of five of the treated eyes. All the patients developed progressive high myopia over the follow-up period.
UNASSIGNED: Anterior segment complications after laser photocoagulation for retinopathy of prematurity may develop later in life. They affect patients\' visual acuity and quality of life and may require treatment.

This study aimed to determine whether the state of retinal vascularization after anti-vascular endothelial growth factor (anti-VEGF) injection can help predict the risk of reactivated retinopathy of prematurity (ROP) requiring treatment and whether repeated ranibizumab injection will be effective in such cases. We retrospectively reviewed 24 infants (43 eyes) who received ranibizumab monotherapy between January 2021 and December 2022. All eyes were classified as having non-retreated ROP or retreated ROP. The state of ROP at the time of treatment, the time required for resolution of plus disease, and the extent of vascularization at 4 and 8 weeks after treatment were analyzed. Extent of temporal retinal vascularization was measured with serial fundus images using disc-fovea distance (DF) unit and disc diameter (DD). Reactivated ROP requiring treatment occurred in six infants (25.0%) and ten eyes (23.3%) after ranibizumab treatment. The mean retreatment interval was 9.0 ± 3.3 weeks (range 4-16). In the retreated ROP group, the time required for the resolution of plus disease after primary injection was longer compared to the control group (13.3 days vs 5.2 days), with a mean ROP regression time of 3.4 weeks. All eyes in the retreated ROP showed retinal vascularization < 0.5 DF from the original site at 4 weeks after injection. In 90% of cases with retreated ROP, the extent of vascularization at 8 weeks after injection was within 1 DF from the original ROP site, and all cases showed reactivation in the posterior Zone II area. The extent of retinal neovascularization in the retreated group was an average of 0.7 DD (vs 1.7 DD) and 1.3 DD (vs 3.3 DD) at 4 and 8 weeks after injection, respectively. After ranibizumab retreatment, only one reactivated case with vitreous traction progressed to focal retinal detachment, while all other cases regressed with peripheral vascular development. The continuation of delayed retinal blood vessel development after ≥ 8 weeks may indicate a high likelihood of reactivated ROP requiring treatment. In the absence of vitreous traction, ranibizumab reinjection is likely to be effective in treating reactivated ROP requiring treatment.

OBJECTIVE: This study aimed to evaluate the treatment efficacy, anatomical outcomes, and refractive outcomes of laser photocoagulation (LPC) and intravitreal ranibizumab (IVR) in the treatment of type I retinopathy of prematurity (ROP) at one-year follow-up.
METHODS: This is a retrospective study on the treatment of type I ROP and aggressive ROP (A-ROP) using LPC or IVR in three Malaysian hospitals providing pediatric ophthalmology services from January 2019 to December 2021. Information on gestational age, birth weight, ROP zone and stage, and underlying comorbidities was collected. Parameters for evaluating treatment efficacy include the time taken to achieve complete regression, the regression rate, and the reactivation rate. The anatomical and refractive outcomes were evaluated at one year of adjusted age.
RESULTS: This study included 92 eyes from 46 infants. Of these, 42 eyes received LPC as the initial treatment, while 50 eyes underwent IVR. A higher percentage of infants with cardiovascular disease were treated with IVR (66.7%) compared to LPC (40%) (p<0.05). However, there were no significant differences in gestational age, birth weight, respiratory distress syndrome, sepsis, or intraventricular hemorrhage between the two treatment groups (p>0.05). Infants treated with LPC had a higher regression rate than those treated with IVR, but they were also significantly more myopic and had worse best-corrected visual acuity (BCVA). Conversely, infants treated with IVR experienced a significantly higher reactivation rate compared to those treated with LPC. Logistic regression analysis showed no significant associations between gestational age, birth weight, plus disease, zone 1 ROP, and the choice of initial treatment with the reactivation of ROP.
CONCLUSIONS: Both LPC and IVR effectively treat type I ROP in infants, with IVR yielding superior anatomical and refractive outcomes and LPC offering a lower reactivation rate. Understanding individual patient characteristics is crucial for treatment selection.

OBJECTIVE: The aims of this research include adapting a patient information tool for whānau (extended family) Māori needs, identifying and reviewing written information provided for the retinopathy of prematurity eye examination (ROPEE) and identifying improvements to ROPEE written information.
METHODS: ROPEE patient information (printed leaflets, website, app) was obtained from all tertiary neonatal intensive care units in Aotearoa New Zealand (Aotearoa). Information was reviewed using an adapted \"20 good-design principles\" guide and given a star rating and Flesch-Kincaid readability score to identify acceptability and usability for patients.
RESULTS: Seven ROPEE information materials were reviewed and varied in alignment with the adapted good-design principles tool. Based on the adapted good-design principles, opportunities were identified in many aspects of the written information for improvement, including words and language, tone and meaning, content and design. The Flesch-Kincaid grade level reading scores ranged from 12-22 years reading age. Written information also did not use te reo Māori (Aotearoa Indigenous language) or extensively use Māori imagery.
CONCLUSIONS: Opportunities exist to improve ROPEE whānau information, including making content more readable, understandable and visually appealing. Optimising the clinical information on ROPEE nationally for Aotearoa will support whānau decision making, and aligning written information with Māori (Indigenous peoples of Aotearoa) is a priority.

UNASSIGNED: Retinopathy of prematurity (ROP) results from postnatal hyperoxia exposure in premature infants and is characterized by aberrant neovascularization of retinal blood vessels. Epithelial membrane protein-2 (EMP2) regulates hypoxia-inducible factor (HIF)-induced vascular endothelial growth factor (VEGF) production in the ARPE-19 cell line and genetic knock-out of Emp2 in a murine oxygen-induced retinopathy (OIR) model attenuates neovascularization. We hypothesize that EMP2 blockade via intravitreal injection protects against neovascularization.
UNASSIGNED: Ex vivo choroid sprouting assay was performed, comparing media and human IgG controls versus anti-EMP2 antibody (Ab) treatment. In vivo, eyes from wild-type (WT) mice exposed to hyperoxia from postnatal (P) days 7 to 12 were treated with P12 intravitreal injections of control IgG or anti-EMP2 Abs. Neovascularization was assessed at P17 by flat mount imaging. Local and systemic effects of anti-EMP2 Ab treatment were assessed.
UNASSIGNED: Choroid sprouts treated with 30 µg/mL of anti-EMP2 Ab demonstrated a 48% reduction in vessel growth compared to control IgG-treated sprouts. Compared to IgG-treated controls, WT OIR mice treated with 4 µg/g of intravitreal anti-EMP2 Ab demonstrated a 42% reduction in neovascularization. They demonstrated down-regulation of retinal gene expression in pathways related to vasculature development and up-regulation in genes related to fatty acid oxidation and tricarboxylic acid cycle respiratory electron transport, compared to controls. Anti-EMP2 Ab-treated OIR mice did not exhibit gross retinal histologic abnormalities, vision transduction abnormalities, or weight loss.
UNASSIGNED: Our results suggest that EMP2 blockade could be a local and specific treatment modality for retinal neovascularization in oxygen-induced retinopathies, without systemic adverse effects.

The vasculature of the retina is exposed to systemic and local factors that have the capacity to induce several retinal vascular diseases, each of which may lead to vision loss. Prostaglandin signaling has arisen as a potential therapeutic target for several of these diseases due to the diverse manners in which these lipid mediators may affect retinal blood vessel function. Previous reports and clinical practices have investigated cyclooxygenase (COX) inhibition by nonsteroidal anti-inflammatory drugs (NSAIDs) to address retinal diseases with varying degrees of success; however, targeting individual prostanoids or their distinct receptors affords more signaling specificity and poses strong potential for therapeutic development. This review offers a comprehensive view of prostanoid signaling involved in five key retinal vascular diseases: retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, retinal occlusive diseases, and uveitis. Mechanistic and clinical studies of these lipid mediators provide an outlook for therapeutic development with the potential to reduce vision loss in each of these conditions.

OBJECTIVE: To compare the results of intravitreal bevacizumab (IVB) monotherapy and combined intravitreal bevacizumab and laser photocoagulation (LPC) therapies applied in the same session to patients with aggressive retinopathy of prematurity (A-ROP) in our clinic.
METHODS: The study included 67 eyes of 37 patients diagnosed with A-ROP and treated. Forty-nine eyes treated with anti-vascular endothelial growth factor agent injection monotherapy for A-ROP treatment were included in the first group. The second group consisted of 18 eyes that received injection therapy and LPC treatment. The clinical findings of the two groups were investigated, and their treatment results were compared.
RESULTS: Recurrence was observed in 19 of the 49 (38%) eyes in the first group, but there was no recurrence in any of the cases in the second group. While only IVB was applied to eight cases with recurrence, the combination of LPC and IVB treatment was applied to 11 cases. A second recurrence was detected in two of the eight cases that had received IVB monotherapy as a treatment for recurrence and in three of the 11 cases that had received LPC and IVB. The treatment outcomes of the two groups did not statistically significantly differ (P = 0.181).
CONCLUSIONS: We consider that the combined simultaneous LPC and IVB treatment we applied in A-ROP cases is an effective approach, particularly for cases where there are concerns about the patient\'s ability to attend follow-up appointments.

OBJECTIVE: To determine the effect of music applied during the ROP examination on pain, comfort, and physiological parameters in preterm infants.
METHODS: The sample of this prospective randomized controlled double-blind experimental study consisted of 28 preterm infants who were examined for ROP of a tertiary hospital in the Neonatal Unit. Data were collected with a Questionnaire, Physiological Parameters Observation Form (PPOF), Revised-Premature Infant Pain Profile (PIPP-R), and Premature Infant Comfort Scale (PICS).
RESULTS: The results revealed that the crying times of the infants in the experimental group were shorter than the infants in the control group. The preterm infants in the experimental group had statistically lower PIPP-R scores during and after the procedure than the PIPP-R scores of the infants in the control group (p < 0.001) and the music applied to the preterm infants resulted in a mean decrease of 3.857 in the post-procedure and pre-procedure PIPP-R scores (p < 0.05). While there was no statistical difference between the pre-procedure and pre-procedural PICS scores of the preterm infants in the experimental and control groups (p = 0.599; p = 117), the post-procedure PICS values of the preterm infants in the experimental group were found to be lower than those of the control group (p < 0.001). It was found that the music applied to preterm infants during the ROP examination resulted in a mean decrease of 1.286 in PICS scores after the procedure and before the procedure (p < 0.05).
CONCLUSIONS: It was determined that the music listened to during the ROP examination decreased the PIPP-R pain scores of preterm infants, had a positive effect on the PICS scores after the procedure, but did not affect the physiological parameters positively.
BACKGROUND: ClinicalTrials.gov Identifier: NCT05263973.

BACKGROUND: Large language models (LLMs) are becoming increasingly important as they are being used more frequently for providing medical information. Our aim is to evaluate the effectiveness of electronic artificial intelligence (AI) large language models (LLMs), such as ChatGPT-4, BingAI, and Gemini in responding to patient inquiries about retinopathy of prematurity (ROP).
METHODS: The answers of LLMs for fifty real-life patient inquiries were assessed using a 5-point Likert scale by three ophthalmologists. The models\' responses were also evaluated for reliability with the DISCERN instrument and the EQIP framework, and for readability using the Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), and Coleman-Liau Index.
RESULTS: ChatGPT-4 outperformed BingAI and Gemini, scoring the highest with 5 points in 90% (45 out of 50) and achieving ratings of \"agreed\" or \"strongly agreed\" in 98% (49 out of 50) of responses. It led in accuracy and reliability with DISCERN and EQIP scores of 63 and 72.2, respectively. BingAI followed with scores of 53 and 61.1, while Gemini was noted for the best readability (FRE score of 39.1) but lower reliability scores. Statistically significant performance differences were observed particularly in the screening, diagnosis, and treatment categories.
CONCLUSIONS: ChatGPT-4 excelled in providing detailed and reliable responses to ROP-related queries, although its texts were more complex. All models delivered generally accurate information as per DISCERN and EQIP assessments.