Background: Secondary full-thickness macular hole (FTMH) in proliferative diabetic retinopathy (PDR) is rare, occurring in only 1-4% of PDR cases. Combined with tractional retinal detachment (TRD), this complication presents significant surgical challenges. The inverted internal limiting membrane (ILM) flap technique remains under-utilized in this specific setting. Case presentation: A 61-year-old Indonesian male with type 2 diabetes (>15 years), chronic kidney disease, and cardiovascular disease presented with sudden vision loss (best-corrected visual acuity 1/300). Examination revealed superior TRD (2-11 o'clock) and large FTMH (CMT 249 micrometers). After intravitreal bevacizumab (August 9th, 2024), he underwent 360-degree pars plana vitrectomy with inverted ILM flap and silicone oil tamponade (August 14th, 2024). Inferior redetachment at 2 months necessitated re-vitrectomy with endolaser and silicone oil evacuation (October 23rd, 2024). At final follow-up (12 weeks post-second surgery), the patient achieved complete retinal reattachment with normalized macular anatomy, visual acuity 1/60, and intraocular pressure 10 mmHg. Conclusion: Despite severe baseline disease and comorbidities, stepwise surgical strategy incorporating preoperative anti-VEGF therapy, comprehensive traction release, inverted ILM flap reconstruction, and staged procedures yielded meaningful anatomical recovery. This case supports inverted ILM flap utility in PDR-related secondary FTMH.

Background: Air travel exposes passengers to environmental stressors, such as reduced cabin pressure and low humidity, which may exacerbate ocular surface conditions, particularly pre-existing dry eye disease (DED). This meta-analysis quantifies the impact of real and simulated aircraft cabin environments on tear film parameters, ocular surface biomarkers, and intraocular pressure (IOP). Methods: Following PRISMA 2020 guidelines, a systematic search (January 2000–March 2026) identified ten eligible studies comprising 445 participants, with two providing complete quantitative data for meta-analytic pooling (10 effect sizes). Results: Using a random-effects model, the overall pooled standardised mean difference (SMD) was 0.97 (95% CI: -0.67 to 2.61), indicating a large but non-significant effect with substantial heterogeneity (I2 = 97.23%). Subgroup analyses revealed a non-significant pooled effect for tear film outcomes (Hedges' g = 0.71), contrasted by a significant elevation in IOP for gas-filled eyes (g = 1.92; p = 0.001). Despite the non-significant overall pooled estimate, individual effect sizes demonstrated large, clinically meaningful reductions in tear break-up time (TBUT) and significant increases in both corneal staining and inflammatory biomarkers (MMP-9 and IL-6). Egger's test showed no publication bias, though GRADE certainty remained low to very low. Conclusion: Aircraft cabin environments induce clinically significant deteriorations in tear film stability, ocular surface integrity, and inflammation, alongside significant IOP elevations in susceptible individuals. These findings underscore the necessity of pre-flight ocular counselling and targeted preventive strategies for at-risk passengers, highlighting the need for future large-scale, standardised investigations.

Background: Fungal keratitis is a major cause of corneal blindness in tropical regions. Microbiological culture often yields negative results in up to 40% of clinically suspected cases, creating diagnostic and therapeutic challenges. This report describes successful management of culture-negative suspected fungal keratitis using epithelial keratectomy combined with intracameral fluconazole injection. Case presentation: A 58-year-old male presented with progressive visual loss in the left eye following mud exposure and irrigation with river water. Examination revealed a 3×3 mm paracentral corneal ulcer with stromal infiltration exceeding one-third depth, satellite lesions, and 1.5 mm hypopyon. Gram stain, potassium hydroxide preparation, and culture were all negative. Based on clinical suspicion of fungal etiology, the patient underwent epithelial keratectomy with intracameral fluconazole injection, supplemented by intensive topical and systemic antifungal therapy. Progressive improvement was observed, with complete hypopyon resolution by day 26 and visual acuity improving from 1/300 to 6/30 over four months. Conclusion: This case demonstrates that timely invasive antifungal intervention guided by clinical judgment can achieve favorable outcomes in culture-negative suspected fungal keratitis. The preservation of useful vision without corneal transplantation is particularly significant in resource-limited settings, underscoring the critical role of clinical decision-making when laboratory confirmation is unavailable.

Background: Psoriasis is a chronic inflammatory skin disorder with increasing evidence supporting the role of the gut-skin axis in its pathogenesis. Recent studies suggest that probiotic supplementation may modulate Th17-mediated immune responses and improve clinical outcomes in psoriasis. Methods: A systematic review and random-effects meta-analysis was conducted using PubMed, Scopus, Web of Science, and Cochrane Library databases (through February 2025). Randomised controlled trials evaluating probiotic supplementation in adult patients with psoriasis were included. The primary outcome was change in Psoriasis Area and Severity Index (PASI) score. Secondary outcomes included inflammatory markers (IL-6, CRP, IL-17) and immunological markers (Foxp3+ regulatory T cells, IL-10, TGF-β). Risk of bias was assessed using the Cochrane Risk of Bias tool (RoB 2), and evidence quality was evaluated using GRADE methodology. Results: Five randomised controlled trials encompassing 268 participants (132 intervention, 136 control) were analysed. The pooled effect size for clinical outcomes (PASI) showed significant improvement favouring probiotic supplementation (Hedges' g = −0.8165; 95% confidence interval [CI], −1.6487 to −0.0483; p = 0.048; I² = 92.45%). Substantial heterogeneity was observed, with the Alshihmani 2025 pilot study demonstrating markedly larger effects on immunological markers (Hedges' g = −5.6963). Subgroup analysis revealed single-strain probiotics (pooled Hedges' g = −0.3487) had smaller effect sizes than multi-strain formulations (pooled Hedges' g = −3.6740). Publication bias assessment via funnel plot and Egger's regression showed no statistically significant asymmetry (p = 0.087). Conclusion: Probiotic supplementation demonstrated statistically significant improvements in clinical outcomes and immunological markers in psoriasis. However, substantial heterogeneity and reliance on small trials limit certainty. The mechanistic evidence supporting gut-skin axis modulation warrants further investigation in adequately powered, long-term randomised controlled trials with standardised outcome measures and strain-specific analysis.

Background: Gout and chronic lymphocytic leukemia (CLL) represent distinct hematologic and rheumatologic pathologies; however, their concurrent presentation presents significant diagnostic and therapeutic challenges. Tumor lysis syndrome and chemotherapy-induced hyperuricemia are recognized complications of hematologic malignancies, yet the manifestation of acute gouty arthritis with crystallographic confirmation in CLL patients remains an underreported clinical scenario requiring careful diagnostic stratification. Case presentation: We present a 69-year-old male farmer with newly diagnosed CLL (stage C, Binet classification) admitted for acute left knee arthritis with effusion, left ankle arthritis, and concurrent community-acquired pneumonia (CAP). Clinical examination revealed articular inflammation characterized by pain, swelling, erythema, warmth, and significant joint effusion with documented flexion limitation and positive bulging sign. Musculoskeletal ultrasound demonstrated double contour sign, synovial hypertrophy, and effusion measuring 5.8 cm in the suprapatellar recess with monosodium urate (MSU) crystal deposition confirmed by polarized light microscopy of synovial fluid (5,350 cells/mm³, 40% polymorphonuclear neutrophils, 60% mononuclear cells, positive MSU crystals). Serum uric acid was elevated at 10.6 mg/dL. The patient was successfully managed with colchicine, methylprednisolone, arthrocentesis, and supportive care while maintaining CLL treatment preparedness. Conclusion: This case illustrates the importance of confirmatory synovial fluid analysis and ultrasound imaging in the diagnosis of acute gout in the context of hematologic malignancy. Optimal management requires careful coordination between rheumatology and hematology-oncology services to prevent therapeutic complications and ensure safe chemotherapy initiation in CLL patients with concurrent acute gouty arthritis and hyperuricemia.

Background: Ultraviolet B (UVB) radiation induces matrix metalloproteinase-1 (MMP-1) expression and epidermal hyperplasia, contributing to photoaging. Rhodomyrtus tomentosa (karamunting) is rich in polyphenolic compounds with documented antioxidant properties, but its in vivo photoprotective effects remain unexplored. Methods: We investigated the effects of R. tomentosa leaf extract cream at varying concentrations (0%, 12.5%, 25%, 50%) on UVB-irradiated Swiss Webster mice (n=4 per group). UVB exposure was standardized at approximately 150 mJ/cm² per session over seven consecutive days. Vitamin E cream served as a positive control. Immunohistochemical staining quantified MMP-1 expression as a percentage of positive cells, while hematoxylin-eosin histology measured epidermal thickness. Results: Kruskal-Wallis testing revealed significant differences in both MMP-1 expression (H=10.43, p=0.015) and epidermal thickness (H=10.88, p=0.012). The 25% extract concentration optimally suppressed MMP-1 expression (mean 45.94% of positive cells) compared to the untreated UVB control (89.53%). A biphasic dose-response pattern emerged, with hormetic effects observed at 50% concentration (76.45%), suggesting polyphenol pro-oxidant activity at excessive concentrations. Epidermal thickness normalized with 25% treatment (71.8 μm) versus UVB control (93.4 μm). Immunohistochemical intensity decreased progressively with treatment intensification through 25%, supporting suppression of MMP-1-mediated collagen degradation. Conclusion: R. tomentosa leaf extract cream at 25% concentration effectively suppresses MMP-1 expression and normalizes UVB-induced epidermal thickening in mice. The hormetic response at higher concentrations highlights the importance of dose optimization in phytotherapeutic development. This work establishes the first in vivo evidence for karamunting leaf extract as a photoprotective agent and supports further clinical translation.

Background: Gas tamponade is a widely used surgical intervention for retinal detachment repair. However, intraocular gas bubbles expand at altitude owing to Boyle's law, potentially causing severe intraocular pressure (IOP) elevation and ischaemic complications. The safety of air travel for patients with residual intraocular gas remains insufficiently characterised. Methods: We conducted a systematic review and meta-analysis of empirical and computational studies examining IOP dynamics during simulated or actual altitude exposure in eyes with intraocular gas. We searched MEDLINE, Embase, Web of Science, Scopus and PubMed Central through March 2024 for peer-reviewed publications without language restrictions. Study selection followed PRISMA 2020 guidelines with predefined eligibility criteria. Data were extracted in duplicate, and risk of bias assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis calculated standardised mean differences (SMD) with 95% confidence intervals (CI). Sensitivity analyses stratified findings by study type. Results: The primary analysis included three empirical studies (n = 47 eyes) showing IOP increase of SMD = 3.03 (95% CI: 2.18–3.89; I² = 17.16%, τ² = 0.11). Sensitivity analysis including all four studies (one computational model) yielded SMD = 4.67 (95% CI: 1.52–7.82; I² = 95.67%, τ² = 9.81). Individual study estimates ranged from SMD = 2.52 (Mills 2001) to SMD = 8.65 (Gsellman 2016, computational). Risk of bias was generally low to moderate. No significant publication bias was detected. Conclusion: Patients with residual intraocular gas who undertake air travel face meaningful IOP elevation at altitude. The risk of anterior segment ischaemic complications warrants careful patient counselling, altitude restriction recommendations, and prophylactic pharmacotherapy. Future prospective studies should evaluate optimal clinical protocols.

Background: Mitral valve disease with concurrent pulmonary hypertension and biventricular dysfunction represents a complex surgical challenge requiring meticulous perioperative management. This case report presents the anesthetic approach to a 43-year-old male with severe mitral regurgitation secondary to posterior leaflet prolapse, Grade III diastolic dysfunction, and intermediate probability pulmonary hypertension undergoing elective mitral valve replacement. Case presentation: The patient presented with 6-month progressive dyspnea, chronic cough, bilateral lower-limb edema, and abdominal distension. Transthoracic echocardiography revealed severe mitral regurgitation with an effective regurgitant orifice area of 2.7 cm², bilateral atrial dilation, moderate tricuspid regurgitation, reduced tricuspid regurgitation jet velocity suggesting intermediate pulmonary hypertension probability, and preserved left ventricular ejection fraction of 68% with severely restrictive diastolic filling pattern. The patient underwent uncomplicated elective mitral valve replacement under general anesthesia with cardiopulmonary bypass. Intraoperative management emphasized hemodynamic stability through judicious fluid administration, careful anesthetic agent selection, and appropriate pulmonary vascular protection strategies. Cardiopulmonary bypass time was 125 minutes with an aortic cross-clamp time of 57 minutes. The postoperative course was uneventful with prompt extubation and discharge from intensive care on postoperative day three. Conclusion: This case illustrates the importance of comprehensive preoperative optimization, multimodal monitoring, and tailored intraoperative management in patients presenting with the complex intersection of severe organic mitral valve disease, pulmonary hypertension, and advanced diastolic dysfunction. The use of sevoflurane-based anesthesia, preservation of systemic vascular resistance, and lung-protective ventilation strategies contributed to favorable perioperative outcomes. This case highlights unique management considerations that may not be extensively detailed in standard anesthetic textbooks and demonstrates successful outcomes despite significant preoperative cardiac compromise.

Background: The development of a broadly protective dengue virus (DENV) vaccine remains a paramount global health priority. Current tetravalent vaccines target the four DENV serotypes. However, intra-serotypic genetic variations, defined as genotypes, present a neglected immunological barrier. Evidence indicates that genotypic divergence critically impairs cross-neutralizing antibody responses, leaving vaccinated individuals vulnerable to circulating heterologous genotypes and severe antibody-dependent enhancement (ADE). This meta-analysis quantifies the impact of DENV genotypic variation on neutralizing antibody efficacy. Methods: A systematic review and meta-analysis adhering to PRISMA guidelines were conducted. Quantitative virological data were extracted from primary studies, focusing on neutralizing antibody titers against homologous versus heterologous DENV genotypes. A DerSimonian-Laird random-effects model calculated the pooled Standardized Mean Difference (SMD) and 95% Confidence Intervals (CI). Heterogeneity was addressed through subgroup analyses (by serotype and host species). A sensitivity analysis employing the Hartung-Knapp-Sidik-Jonkman (HKSJ) adjustment verified robustness. Risk of bias was evaluated utilizing RoB 2 and SYRCLE tools. Results: Ten controlled studies met the inclusion criteria. The pooled analysis revealed a severe, statistically significant reduction in neutralization capacity against heterologous genotypes compared to homologous strains, yielding an overall SMD of -1.52 (95% CI: -1.95 to -1.09, p < 0.001). High initial heterogeneity (I2 = 84.1%) was partially resolved by stratifying by serotype; the DENV-2 subgroup demonstrated the most profound neutralization deficit (SMD = -1.78, I2 = 42.5%). Sensitivity analyses confirmed the stability of the pooled effect. Conclusion: Vaccine-induced neutralizing responses are significantly attenuated against heterologous DENV genotypes. The prevailing serotype-level vaccine paradigm is insufficient for comprehensive global immunity. Next-generation vaccine designs must incorporate conserved, pan-genotypic epitopes to prevent intra-serotypic immune evasion and subsequent ADE-mediated severe disease.