Search Results (802)

The Hippo–Yorkie (Yki) signaling pathway is a conserved regulator of tissue growth, and its dysregulation leads to excessive growth and tumorigenesis. Although several microRNAs (miRNAs) have been implicated in Hippo pathway regulation, how they modulate Yki activity in vivo remains incompletely understood. Here, we identify miR-137 as a suppressor of Yki-driven overgrowth in a Drosophila model. A functional miRNA screen revealed that miR-137 overexpression markedly suppresses Yki-induced eye overgrowth, whereas inhibition of miR-137 enhances eye overgrowth phenotypes. Through bioinformatic prediction and genetic screening, we identified Drep1 as a candidate downstream factor associated with miR-137 function. RNAi-mediated depletion of Drep1 phenocopies the suppressive effects of miR-137, whereas Drep1 overexpression enhances Yki-driven tissue overgrowth and proliferation. Consistent with these phenotypes, miR-137 overexpression or Drep1 depletion reduces the expression of canonical Yki target genes, including Diap1 and Expanded, indicating decreased Yki transcriptional output. Importantly, Drep1 knockdown was associated with reduced Yki immunostaining in a complementary wing-disk context, suggesting a potential link between Drep1 and Yki-associated signaling. Consistent with this, miR-137 also reduced the expression of ICAD, the mammalian homolog of Drep1, providing preliminary evidence that miR-137 may regulate ICAD expression in mammalian cells. Together, these findings support a potential regulatory relationship between miR-137 and Drep1 that modulates Yki-driven eye overgrowth and reveal an additional layer of Hippo pathway regulation in vivo. Full article

Objective: This study aimed to evaluate the predictability of baseline optical coherence tomography angiography (OCTA) metrics utilizing a specialized capillary–large vessel segmentation analysis framework in patients with diabetic macular edema (DME) undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: Forty-two treatment-naïve eyes with DME receiving three monthly loading anti-VEGF injections were included. Superficial capillary plexus (SCP) images from 3 × 3 mm OCTA scans were processed to isolate the capillary network from the large vessels via image processing. Vessel density and skeleton density were extracted for the total, large-vessel, and capillary components. Multiple linear and logistic regression models were used to identify independent predictors of post-treatment best-corrected visual acuity (BCVA) and “good visual outcome” (≥3-line improvement or final BCVA of 20/40 or better). Results: Following three monthly anti-VEGF injections, the mean BCVA significantly improved from 0.57 ± 0.36 to 0.37 ± 0.30 LogMAR (p < 0.0001), and the mean central retinal thickness decreased from 424.3 ± 117.7 μm to 316.9 ± 84.7 μm (p < 0.0001). The proportion of patients who achieved a good visual outcome was 73.8%. Baseline central retinal thickness was associated with baseline BCVA (p = 0.049) but not predictive of post-treatment BCVA (p = 0.38) or good visual outcomes (p = 0.79). Baseline capillary vessel density was identified as a significant independent predictor of post-treatment BCVA (p = 0.024), whereas total and large-vessel metrics were not. Capillary vessel density was also the only significant predictor of good visual outcomes (p = 0.044). Conclusions: Baseline capillary vessel density is a robust predictor of visual prognosis after anti-VEGF therapy in patients with DME, underscoring the importance of capillary network integrity in functional recovery. Full article

Understanding the early life history of the endangered largemouth bronze gudgeon (C. guichenoti) is crucial for optimizing artificial rearing and conservation strategies. To provide a unified scientific basis for these efforts, this study characterized the ontogeny of C. guichenoti larvae from hatching to 30 days post-hatch (dph) by integrating analyses of allometric growth, digestive histology, and enzyme activities. Morphometric analysis revealed that total length increased exponentially with age. Positive allometric growth was observed in swimming organs (pectoral, dorsal, and caudal fins) and eye diameter, indicating a priority in developing locomotion and sensory capabilities for survival in lotic environments. Histological examination showed that the digestive tract became patent by 4 dph, and functional structures were established by 5 dph, coinciding with yolk sac absorption and the initiation of exogenous feeding. The digestive system reached near-adult maturity by 20 dph. Enzyme activity profiles showed that trypsin activity increased continuously, peaking at 30 dph, while amylase and alkaline phosphatase peaked at 20 dph. Lipase activity remained low until a slight increase at 30 dph. These results indicate that C. guichenoti larvae adopt a “locomotion-first” strategy, with the digestive system becoming functional at 5 dph and maturing by 20 dph. These findings collectively define the critical windows for artificial propagation, specifically guiding the timing of initial feeding and feed formulation. Full article

Introduction: Teprotumumab (Tepezza^®), an insulin-like growth factor-1 receptor (IGF-1R) antagonist, is the first FDA-approved targeted therapy for thyroid eye disease (TED). While effective for reducing proptosis and inflammation, increasing post-marketing evidence has linked teprotumumab to auditory adverse events. IGF-1 signaling is essential for cochlear maintenance and neuroprotection; therefore, systemic IGF-1R inhibition presents a biologically plausible mechanism for ototoxicity. Despite growing recognition of these effects, no standardized approach exists for audiologic assessment or monitoring of patients receiving teprotumumab. This review aimed to (1) summarize proposed mechanisms and the reported spectrum of teprotumumab-related auditory effects, (2) evaluate current methods used to assess and monitor these patients, and (3) identify areas of consensus and ongoing uncertainty. Methods: An updated narrative review of the literature was conducting using PubMed, CINAHL, and Google Scholar using Boolean strings targeting teprotumumab exposure and hearing-related outcomes. Studies from 2022 onward were identified using Boolean search strings targeting teprotumumab exposure and hearing-related outcomes. Peer-reviewed English language studies reporting audiometric findings were eligible for inclusion. Results: Ten studies met inclusion criteria. Reported effects most commonly included bilateral high-frequency SNHL, tinnitus, and aural fullness, typically emerging after three to six infusions. Many cases demonstrated persistent deficits despite drug discontinuation. Baseline audiometric assessment was not uniformly reported across studies, and monitoring protocols varied considerably, with inconsistent incorporation of speech testing and immittance measures. Conclusions: Teprotumumab-associated ototoxicity is increasingly recognized and potentially irreversible. Current evidence is insufficient to guide standardized monitoring. Prospective studies are urgently needed to establish evidence-based audiologic surveillance protocols. Full article

Repeated low-level red light (RLRL) has been reported to control myopia progression clinically. Given safety concerns with laser sources, light-emitting diodes (LED)-sourced red light represents a promising alternative. This study investigated the effects of LED-sourced red light (RL) on cellular response in vitro and ocular growth in normal and lens-induced myopic chicks. In vitro, the mouse photoreceptor 661W cell line was exposed to 625 and 664 nm LED-sourced RL (3 min, twice daily) for 3 days, and cytochrome c oxidase (CCO) activity and cell viability were assessed. In vivo, chicks were randomly assigned to normal visual conditions or monocular −5D lens-induced myopia (LIM). Treatment groups received 664 nm LED-sourced RL (30 min, twice daily) at low, moderate, or high intensities for 10 days. In vitro, LED-sourced RL at 664 nm more effectively activated CCO and enhanced cell viability in 661W cells than RL at 625 nm and white light. In vivo, low-intensity RL exposure of 10 days significantly inhibited vitreous chamber depth (VCD) and axial length (AL) elongation compared to the normal light group (p < 0.05) in normally growing chicks but showed no significant effect in LIM eyes. By contrast, moderate- and high-intensity RL exposure for 10 days attenuated myopia progression in LIM eyes, as reflected by slower VCD and AL elongation and less myopic shift, compared to the normal light group (all p < 0.05). Notably, high-intensity RL also protected the untouched fellow eyes of the LIM chick models against myopic shift and excessive elongation. LED-sourced RL at 664 nm was effective in activating CCO, reducing apoptosis, and promoting cell viability. In chick models, it can also inhibit ocular growth in both normally growing and −5D lens-induced myopic chicks. Full article

The use of agricultural by-products as feed is essential for sustainable animal husbandry. This study assessed the effects of substituting whole-plant corn silage with a mixed silage of cotton stalks and grape pomace on growth, serum biochemistry, and jejunal metabolomics in Suffolk rams. In this experiment, 135 rams (6-mo, 30.55 kg BW) were allocated to 0%, 50%, or 100% replacement (CG, EG50, EG100) and fed for 120 d after a 15-d adaptation. Compared with the CG, average daily gain improved by 27.3% and 17.5%, and feed conversion improved by 30.8% and 15.4% in EG50 and EG100 (p < 0.01). Compared with CG, the levels of BUN, TNF-α and IL-1β in serum of EG50 and EG100 were significantly decreased. The levels of IgG, IgM, IL-4, antioxidant enzymes and total antioxidant capacity were significantly increased (p < 0.05). Subsequently, the slaughter performance and jejunal content metabolome of CG and EG50 were further detected and analyzed. The results indicated that the live weight, eye area and muscle crude protein content of EG50 were extremely significantly higher than those of CG (p < 0.01). In jejunal contents, 31 differential metabolites (EG50 vs. CG) were enriched in ABC transporters, branched-chain amino acid biosynthesis, mineral absorption, purine and biotin metabolism, and glucagon signaling. In conclusion, substituting corn silage with the mixed silage promotes growth, improves antioxidant and immune status, reduces serum urea nitrogen, enhances muscle protein deposition (EG50), modulates intestinal nitrogen, purine, lipid, and carbohydrate metabolism (EG50), and supports sustainable meat sheep production. Full article

Background: Neovascular age-related macular degeneration (nAMD) remains a leading cause of irreversible central vision loss. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed management, pivotal trials enrolled exclusively treatment-naïve patients, leaving clinicians without pooled evidence to guide switching decisions in previously treated eyes. This systematic review and meta-analysis assessed real-world visual, anatomical, durability, and safety outcomes following switching to aflibercept 8 mg in previously treated nAMD. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, CENTRAL, Scopus, and Google Scholar through April 2026. Studies reporting switching to aflibercept 8 mg with change in best-corrected visual acuity (BCVA), central subfield thickness (CST), or treatment interval were included. Continuous outcomes were pooled using random-effects models with Hartung–Knapp–Sidik–Jonkman adjustment; proportions were estimated using generalized linear mixed models. Methodological quality was evaluated using the JBI Critical Appraisal Checklist for Case Series. Certainty of evidence was assessed using GRADE. The protocol was registered with PROSPERO (CRD420261371334). Results: Twenty-one studies met inclusion criteria. BCVA remained stable (WMD: −0.017 logMAR; 95% CI: −0.027 to −0.007; +0.83 ETDRS letters; I² = 0%). CST decreased significantly (WMD: −21.5 µm; 95% CI: −29.3 to −13.7; I² = 56.0%), and treatment intervals extended by +1.79 weeks (95% CI: +1.32 to +2.27; I² = 74.3%). Intraretinal and subretinal fluid each resolved in 37.5% of eyes. Intraocular inflammation was rare across 9959 treated eyes, though this pool was not restricted to switched eyes, with no confirmed retinal vasculitis. Sensitivity analyses confirmed robustness across all co-primary estimates. GRADE certainty was low for BCVA and very low for CST and treatment interval. Conclusions: Low-certainty evidence suggests that switching to aflibercept 8 mg preserves visual acuity, while very-low-certainty evidence suggests reductions in central subfield thickness and modest extension of treatment intervals. Intraocular inflammation was rare, though safety denominators included non-switch eyes. These findings provide preliminary pooled estimates to inform switch decisions in previously treated eyes. Full article

Background: Intravitreal injections (IVI) are widely used for the management of retinal diseases, yet younger adults are underrepresented in clinical trials and real-world reports. Data on the etiologic distribution and treatment patterns of IVI in patients aged ≤50 years remain limited. This study aimed to characterize the indications, treatment strategies, and visual outcomes of IVI in this age group. Material and Methods: Retrospective, single-center observational study including adults aged 18–50 years who received IVI between January 2020 and December 2023 at a tertiary referral hospital in Spain. Demographic data, diagnosis, treatment modality, regimen, number of injections and best-corrected visual acuity (BCVA) were collected. One eye per patient was included for analysis. Visual outcomes were assessed as change in logMAR BCVA between baseline and final follow-up. Results: A total of 122 patients were included. The most frequent indications were diabetic macular edema (29.5%), macular neovascularization of various etiologies (21.3%), retinal vein occlusion (13.9%) and uveitis (9.8%). Anti-vascular endothelial growth factor (anti-VEGF) agents were used in 80.3% of eyes, corticosteroids in 6.6% and combination therapy in 13.1%. The mean number of injections per patient was 6.0 ± 5.3 over a mean follow-up of 3.0 ± 2.5 years. Overall BCVA improved significantly from 0.50 ± 0.59 to 0.38 ± 0.50 logMAR (p = 0.012). Conclusions: IVI in adults ≤ 50 years is uncommon but encompasses a broad etiologic spectrum. Diabetic macular edema and macular neovascularization of diverse etiologies were the leading indications. Anti-VEGF therapy represented the main treatment modality in this cohort. Full article

Background/Objectives: Wound infections represent a major category of healthcare-associated infections (HAIs) that interrupt the wound healing process, resulting in delayed wound healing and increasing the incidence of mortality, morbidity and healthcare costs. With the emergence of antibiotic resistance, there is an urgent need to find alternative therapeutic strategies capable of overcoming antibiotic resistance while simultaneously promoting wound healing. Previously, we synthesized iron oxide nanoparticles stabilized with cetyltrimethylammonium bromide (IONPs-CTAB), reported their antimicrobial activity against selected multidrug-resistant bacteria (MDR-bacteria) and SARS-CoV2 virus, and addressed their biocompatibility with the skin and eyes of rabbits. Therefore, it is hypothesized that IONPs-CTAB might be a promising alternative therapeutic agent for management of infected wounds. Methods: IONPs-CTAB were synthesized, and their successful synthesis was confirmed by FTIR, DSC-TGA, and XPS. Their antibacterial activity against three MDR-bacteria, Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), isolated from infected wounds was investigated via the microdilution test to determine MIC/MBC, and a time–kill curve study was also performed. Subsequently, an in vivo study was conducted to assess their wound healing activity on both non-infected and infected wounds. Results: IONPs-CTAB had MIC and MBC values ranging from 125 to 250, and 500 to 1000 µg/mL, respectively. The time–kill curve study showed an effective control of bacterial growth for all tested bacteria. The vivo study demonstrated the superior wound healing activity of IONPs-CTAB compared to standard treatment on both non-infected and infected wounds. This was further confirmed by histopathological examination and biochemical analysis. Conclusions: IONPs-CTAB might be a good therapeutic alternative for the management of infected and non-infected wounds. However, future studies are still required to assess their long-term safety and the possibility of their extravasation to systemic circulation, with their potential accumulation in various organs after a long-term application. Full article

The cornea and conjunctiva are particularly susceptible to injury and adverse effects, either induced by topically applied drugs or excipients used in ophthalmic formulations. Surfactants and cosurfactants are important for producing topical eye formulations of poorly water-soluble drugs, yet they have not been always used in concentrations that are nontoxic and non-irritating to the ocular surface. This study systematically compared the cytotoxicity and ocular irritation potential of commonly used ophthalmic surfactants and cosurfactants under standardized experimental conditions using complementary in vitro and ex vivo ocular safety models. The ocular irritation of Tween 80, Cremophor EL, polyethylene glycol 400 (PEG 400) and propylene glycol (PG) was examined using the HET-CAM (conjunctival) and BCOP (corneal) eye assays. The toxic effect of the four excipients after 24 h on HLE-B3 cell growth was investigated and found to be dose-dependent. The highest tolerable concentrations of Tween 80 and Cremophor EL were 0.25% (w/w), whereas PEG 400 and PG were non-toxic at 5% (w/w). Tween 80 and Cremophor EL at 0.25% (w/w) and PEG 400 and PG at 5% (w/w) were all devoid of conjunctival and corneal irritation. This study systematically compared the cytotoxicity and ocular irritation potential of commonly used ophthalmic surfactants and cosurfactants under standardized experimental conditions using complementary in vitro and ex vivo ocular safety models. Interestingly, there is strong agreement between the results obtained using the HET-CAM and BCOP assays, where both have been successfully used to evaluate the potential for ocular irritation caused by the aforementioned excipients. Full article

Despite the widespread use of phytase in swine diets, there is a need to update the current evidence on its effects on performance, carcass traits, and economic outcomes. This meta-analysis evaluated the impact of phytase supplementation on growth performance, carcass traits, and economic returns in growing–finishing pigs, combining meta-analysis with economic modeling. A systematic review (Web of Science, ScienceDirect, PubMed, and Scopus) revealed 1049 studies, 17 of which met the inclusion criteria (PRISMA). Three treatments were considered: a basal diet (BD), a reduced-P diet without phytase (DRP), and a reduced-P diet with phytase (DRP + P), with effect sizes expressed as weighted mean differences (WMDs). The meta-analysis included performance traits (daily feed intake, DFI; daily weight gain, DWG; feed conversion, FC; and final weight, FW) and carcass traits (carcass weight, CW; carcass yield, CY; backfat thickness, BT; loin eye area, LEA; lean meat percentage, LMP; and lean meat yield, LMY). With respect to BD vs. DRP, P reduction impaired performance and decreased ADG, DFI, and final weight (p < 0.001), especially at reductions ≥0.12%. In DRP + P vs. BD, phytase had no significant effects on performance (WMD = 0.008 kg/day) or carcass traits. In DRP + P vs. DRP, phytase improved performance (ADG: +0.068 kg/day; DFI: +0.106 kg/day; FW: +4.630 kg; FC: −0.115; p < 0.001), with stronger effects in males and at greater P reductions. In DRP + P vs. DB, carcass traits were not significantly affected, whereas DB vs. DRP reduced LEA (WMD = −1.820, p < 0.00), and DRP + P vs. DRP produced subgroup-dependent changes in CW, LEA, and LMY according to sex, phytase source, and diet composition. Economically, phytase increased profit by up to US$ 2.66 (vs. BD) and US$ 5.14 (vs. DRP), remaining advantageous even with enzyme price increases of up to 4×. Overall, phytase supplementation improved performance and economic returns, representing an effective strategy for the development of swine production systems. Full article

As an important aquaculture bivalve, the Pacific oyster (Crassostrea gigas) undergoes a metamorphosis process during its embryonic development. The mortality rate of the eye-spot larva during the metamorphosis and settlement stage is relatively high, which urgently needs to be solved. Glutathione (GSH), as a key antioxidant and immune regulator in organisms, plays an important role in the growth, development, and immune defense of marine invertebrates. Analysis of oyster transcriptome data revealed that the expression of key enzyme-producing GSH, Glutathione S-transferase Kappa 1, reached the highest level at the pediveliger larvae (the stage just before eye-spot larvae), suggesting its important role in the larval settlement process. This study investigated the effects of reduced glutathione supplementation in pediveliger larvae on the settlement metamorphosis and immune capacity of eye-spot larvae. The results showed that high concentrations of glutathione (100 μmol/L, 500 μmol/L) significantly reduced the larval eye-spot rate and settlement rate, with larvae in the 500 μmol/L group nearly all dead after 48 h. Meanwhile, low-concentration GSH (7 μmol/L) could significantly increase the settlement rate of larvae, which was 1.17 times (p < 0.05) that of the control group. When the larvae developed to 1-month-old eye-spot larvae, the survival rate of larvae in the low GSH group significantly increased (38.42 ± 15.98%) after Vibrio splendidus stimulation, while they were almost all dead in the control group. Low GSH could also significantly increase lysozyme LZM activity (by 1.39 times, p < 0.05) and Cu/Zn-SOD activity (by 1.15 times, p < 0.05). Gene expression analysis found that low GSH promoted expressions of larval settlement and metamorphosis-related genes, including ecdysone receptor, P450, and calmodulin. Treatment with low GSH also enhanced the expressions of immune genes of SOD, CAT, and LZM. In summary, a low glutathione supplement can promote the settlement process of oyster eye-spot larvae and enhance disease resistance. These findings reveal the role of glutathione in the metamorphosis and settlement of oyster larvae, providing a scientific basis for optimizing techniques for oyster seedling cultivation. Full article

Pork production is closely linked to skeletal muscle growth and anabolic processes. This study investigated the effects of dietary supplementation with a multi-strain probiotic (Lactiplantibacillus plantarum, Streptococcus thermophilus, and Bacillus subtilis) on the growth performance, carcass traits, gut microbiota, and potential signaling pathways in growing pigs. A total of 144 weaning piglets (28 days old) were randomly allocated to two groups and fed diets with or without probiotics (0.1%) for 18 weeks. Pigs fed with probiotics showed significantly improved feed efficiency (p < 0.05) and greater muscle mass in the loin eye, arm shoulder, and blade shoulder regions. Microbiome analysis revealed significant enrichment of short-chain fatty acid (SCFA)-producing taxa, including Acidaminococcus, Allisonella, Dialister, and Megasphaera, alongside an increased cecal butyrate level in pigs fed probiotics. Integrated fecal microbiome and serum metabolomics analysis demonstrated that the metabolite profile was substantially altered by the supplementation of probiotics. Additionally, serum insulin levels, expression of the bile acid receptor tgr5, and upstream genes in the PI3K/Akt/mTOR pathway (igf1r, insr, and pi3k) were significantly upregulated (p < 0.05). Collectively, these results suggest that a multi-strain probiotic supplementation may be a promising strategy for improving muscle deposition and feed efficiency in commercial pig production. Full article

Background: Diabetic macular edema (DME) is a leading cause of vision loss. Although real-world data on faricimab, a bispecific antibody targeting vascular endothelial growth factor-A and Angiopoietin-2, are expanding, its long-term durability in routine clinical practice has not yet been fully established. We evaluated effectiveness, anatomic response and treatment durability of first-line faricimab in treatment-naïve DME. Methods: We conducted a single-center, retrospective cohort study of treatment-naïve DME eyes initiated on intravitreal faricimab (August 2023–October 2024) in a real-world setting. After a loading phase, eyes were managed with a treat-and-extend or pro re nata regimen. The primary endpoint was retreatment interval at 48 weeks. Secondary endpoints were retreatment interval at weeks 12, 24 and 36; change in visual acuity (VA); central subfield thickness (CST); and optical coherence tomography (OCT) fluid. Results: Fifty-two eyes from 40 consecutive patients were included (baseline VA 65.96 ± 13.55 letters; CST 426.56 ± 106.72 µm). Mean injections were 4.02 ± 1.11 between months 1–6 and 1.90 ± 0.98 between months 7–12. VA improved by +8.46, +7.57, +7.65 and +7.72 letters at 12, 24, 36, and 48 weeks (all p < 0.0001), respectively. Relative CST decreased by −28.05%, −27.01%, −29.46% and −25.22% at the same time points (all p < 0.0001). At week 48, 15.4% of eyes were on a treatment interval of less than 12 weeks, 23.1% were between 12 and 16 weeks, and 46.1% were on 16 or more weeks; 15.4% were managed PRN. Conclusions: First-line faricimab in treatment-naïve DME in a real-world setting yielded clinically meaningful and durable extensions in treatment intervals, alongside sustained functional and anatomical improvements. Full article

Background: Retinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and myopic choroidal neovascularization (mCNV), often require repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Although ranibizumab is well established, long-term affordability remains challenging. Objective: To compare the functional, anatomical, treatment-burden, and safety outcomes of biosimilar ranibizumab (Ranieyes) and innovator ranibizumab (Lucentis/Accentrix) in routine clinical practice. Methods: This multicenter retrospective comparative study included 4997 eyes from 3577 patients treated across five tertiary eye-care centers in India. The biosimilar group comprised 2543 eyes from 1812 patients (10,893 injections), and the innovator group comprised 2454 eyes from 1765 patients (10,136 injections). Eligible indications were nAMD, DME, BRVO, CRVO, mCNV, and an exploratory miscellaneous preoperative adjunct subgroup. BCVA (logMAR), central subfield thickness (CST; µm), injection burden, and ocular/systemic adverse events were assessed over 24 months. Results: Both groups showed early improvement in BCVA and CST across the major disease categories, followed by long-term stabilization. Between-group differences were generally small, not sustained over follow-up, and of limited clinical magnitude. Serious ocular and systemic adverse events were rare in both groups, and no new safety signal emerged. Conclusions: In this large real-world cohort, the biosimilar ranibizumab Ranieyes showed outcomes broadly comparable to innovator ranibizumab across the major retinal disease subgroups, although these findings should be interpreted as observational comparative evidence rather than formal proof of equivalence. Full article