Artificial intelligence-based fluid quantification and associated visual outcomes in a real-world, multicentre neovascular age-related macular degeneration national database.

AIM: To explore associations between artificial intelligence (AI)-based fluid compartment quantifications and 12 months visual outcomes in OCT images from a real-world, multicentre, national cohort of naïve neovascular age-related macular degeneration (nAMD) treated eyes. METHODS: Demographics, visual acuity (VA), drug and number of injections data were collected using a validated web-based tool. Fluid compartment quantifications including intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) in the fovea (1 mm), parafovea (3 mm) and perifovea (6 mm) were measured in nanoliters (nL) using a validated AI-tool. RESULTS: 452 naïve nAMD eyes presented a mean VA gain of +5.5 letters with a median of 7 injections over 12 months. Baseline foveal IRF associated poorer baseline (44.7 vs 63.4 letters) and final VA (52.1 vs 69.1), SRF better final VA (67.1 vs 59.0) and greater VA gains (+7.1 vs +1.9), and PED poorer baseline (48.8 vs 57.3) and final VA (55.1 vs 64.1). Predicted VA gains were greater for foveal SRF (+6.2 vs +0.6), parafoveal SRF (+6.9 vs +1.3), perifoveal SRF (+6.2 vs -0.1) and parafoveal IRF (+7.4 vs +3.6, all p<0.05). Fluid dynamics analysis revealed the greatest relative volume reduction for foveal SRF (-16.4 nL, -86.8%), followed by IRF (-17.2 nL, -84.7%) and PED (-19.1 nL, -28.6%). Subgroup analysis showed greater reductions in eyes with higher number of injections. CONCLUSION: This real-world study describes an AI-based analysis of fluid dynamics and defines baseline OCT-based patient profiles that associate 12-month visual outcomes in a large cohort of treated naïve nAMD eyes nationwide.

Diagnosis and Management of Patients With Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Delphi Consensus Exercise.

Geographic atrophy (GA) is a progressive and irreversible retinal disease with no comprehensive recommendations for diagnosis or monitoring. We used a Delphi approach to determine consensus in key areas around diagnosis and management of GA. A steering committee of eight retina specialists developed two sequential online surveys administered to eye care professionals (ECPs). Consensus was defined as agreement by ≥ 75% of respondents. Up to 177 ECPs from eight countries completed one or both surveys. Consensus was achieved in several topics related to diagnostic imaging, including the use of optical coherence tomography, and the urgent need for treatments and beneficial interventions to reduce the associated burden. Currently, low-vision aids and smoking cessation are considered the most beneficial interventions. We demonstrate consensus for diagnosis and management of patients with GA including best practices in patient identification and monitoring, and unmet needs. [Ophthalmic Surg Lasers Imaging Retina 2023;54:589-598.].

Retinal phototoxicity after macular hole surgery in a patient under paclitaxel.

BACKGROUND: The purpose is to report the second case, to our knowledge, of suspected paclitaxel-induced phototoxic maculopathy following pars plana vitrectomy surgery. CASE PRESENTATION: 63-year-old phakic female who underwent an uneventful phaco-vitrectomy to treat a complete macular hole, developing macular phototoxicity in the post-operatively period that could not be explained by the surgery itself and could only be attributed to a possible photosensitization induced by the previous use of paclitaxel. CONCLUSIONS: The use of paclitaxel has been widely extended as a chemotherapy drug to treat breast cancer. It works by altering the intracellular microtubular reorganization and, based on this mechanism of action, photosensitivity has been previously described. We report a case of suspected paclitaxel-induced macular phototoxicity following ocular endoillumination during vitrectomy surgery.

Early-switch versus late-switch in patients with diabetic macular edema: a cost-effectiveness study.

BACKGROUND: To evaluate the cost-effectiveness of early- versus late-switch to the intravitreal-dexamethasone implant (DEX-i) in patients with diabetic macular edema (DME) who did not adequately respond to vascular endothelial growth factor inhibitors (anti-VEGF). METHODS: Retrospective analysis of a multicenter Clinical Data Registry. The registry included DME eyes who received 3 intravitreal anti-VEGF injections (early-switch) or > 3 intravitreal anti-VEGF injections (late-switch) before switching to DEX-i injections. The primary outcome was to estimate the incremental cost needed to obtain a best-corrected visual acuity (BCVA) improvement ≥ 0.1 or a central-retinal thickness CRT ≤ 250 µm. RESULTS: The analysis included 108 eyes, 32 (29.6%) and 76 (70.4%) in the early- and late-switch groups, respectively. Early-switch strategy was associated with a cost saving of €3,057.8; 95% CI: €2,406.4-3,928.4, p < 0.0001). Regarding incremental-cost-effectiveness ratio, late-switch group was associated with an incremental cost of €25,735.2 and €13,533.2 for achieving a BCVA improvement ≥ 0.1 at month 12 and at any of the time-point measured, respectively. At month 12, 38 (35.2%) eyes achieved a BCVA improvement ≥ 0.1. At month 12, 52 (48.1) eyes had achieved a CRT ≤ 250 micron. As compared to baseline, the mean (95% CI) CRT reduction was - 163.1 (- 212.5 to - 113.7) µm and - 161.6 (- 183.8 to - 139.3) µm in the early-switch and late-switch groups, respectively, p = 0.9463. CONCLUSIONS: In DME eyes, who did not adequately respond to anti-VEGF, switching to DEX-i at early stages (after the first 3-monthly injections) was found to be more cost-effective than extending the treatment to 6-monthly injections of anti-VEGF.

OPHTHALMOLOGIC INVOLVEMENT IN PATIENTS WITH HEREDITARY TRANSTHYRETIN AMYLOIDOSIS.

PURPOSE: The aim of this study was to determine the ophthalmologic involvement in patients with hereditary transthyretin amyloidosis and its correlation with the mutations described in the literature. METHODS: Cross-sectional, noninterventional study. Fifty-two eyes of 26 consecutive patients diagnosed with hereditary transthyretin amyloidosis who visited the Puerta de Hierro-Majadahonda University Hospital from September 2019 to March 2022. All patients underwent complete ophthalmologic examination and multimodal imaging. Cardiologic, neurologic, digestive, and renal examinations were also recorded. RESULTS: Eighteen eyes of the total (34.61%) showed amyloid-related ocular involvement, vitreous amyloid deposits being the most common ocular manifestation (18/52). Statistically significant differences were found for the presence of vitreous amyloid deposits ( P < 0.01), crystalline amyloid deposits ( P < 0.05), parenchymal amyloid deposits ( P < 0.01), and vascular alterations ( P < 0.01) when comparing affected and unaffected eyes. Moreover, affected eyes showed worse best-corrected visual acuity ( P < 0.01). CONCLUSION: Ocular manifestations are present in a substantial number of patients with ATTR that could potentially lead to devastating consequences to patients' best-corrected visual acuity and quality of life. Therefore, it is important to emphasize the importance of multidisciplinary management and ophthalmologic assessment, follow-up and surgical treatment when necessary. To the best of our knowledge, this represents the largest series in Spain of amyloidosis' ophthalmologic involvement.

Bilateral Choroidal Detachment in the Absence of Previous Intraocular Surgery.

The aim of this report was to present a case of bilateral choroidal detachment following treatment with topical therapy dorzolamide/timolol without history of previous surgery. An 86-year-old woman, with intraocular pressures of 40.00/36.00 mm Hg, was treated with preservative-free double therapy with dorzolamide/timolol. One week later, she presented with bilateral vision loss and irritative symptoms in the face, scalp, and ears, with well controlled pressures. The anterior exam showed LOCS III N4C3 cataracts, and the fundus and ultrasound exams revealed a bilateral infero-temporal choroidal detachment in the absence of neoplasia or other systemic cause. One week in absence of hypotensive treatment and receiving topical prednisolone, she showed reattachment of the choroidal detachment. Six months after cataract surgery, the patient remains stable, without choroidal effusion regression. Hipotensive treatment following chronic angle closure can lead to choroidal effusion similar to cases of acute angle closure treated with oral carbonic-anhydrase inhibitors. The combined strategy of removing hipotensive treatment and topical corticosteroids could be useful for the initial management of choroidal effusion. Also, performing cataract surgery after choroidal reattachment can help with stabilization.

Economic burden of age-related macular degeneration in routine clinical practice: the RAMDEBURS study.

PURPOSE: To describe and evaluate the main direct health costs, in routine clinical practice, of age-related macular degeneration (AMD) patients, from hospital perspective, in Spain. METHODS: Retrospective, multicenter, and observational study conducted on five third-level Spanish hospitals, between December 2018 and December 2019. The study included patients who were diagnosed of AMD before December 2018. Direct healthcare costs were obtained from a Spanish database. Study variables included demographic and clinical variables, and resources, such as treatment, diagnostic tests, medical examination, and surgery. Among the 1414 screened AMD patients, 1164 patients were included. In the overall study patients, the total cost was €5,386,511.0, with a mean cost per patient of €4627.6 ± 2383.9. The largest cost items were diagnostic examinations (€2.832.902,0) and vascular endothelial growth factor inhibitors (anti-VEGF) treatment (€2.038.257,2). Bevacizumab was administered to 325 (27.9%) patients, ranibizumab to 328 (28.2%), and aflibercept to 626 (53.8%); 115 (10.7%) patients received two anti-VEGF treatments, while 90 (7.7%) did not receive any. Over the course of the study, a total of 6,057 anti-VEGF injections were administered, with a mean (95% confidence interval) of 4.8 (4.4-5.2) injections per patient. Regarding safety, 29 patients experience injection-related adverse events, among them 12 patients had cataract and 11 ones elevated intraocular pressure (IOP). The incidence of endophthalmitis was 0.5% (6/1164). CONCLUSIONS: AMD was associated with considerable healthcare costs for regional healthcare systems. Diagnostic examinations, particularly OCT examinations, and anti-VEGF treatment represented the largest cost items.

Results of dexamethasone intravitreal implant (Ozurdex) in diabetic macular edema patients: Early versus late switch.

PURPOSE: To assess the functional and anatomical outcomes of intravitreal dexamethasone implant Ozurdex® in eyes with diabetic macular edema that did not adequately respond to vascular endothelial growth factor inhibitors. METHODS: Multicenter, retrospective, and real-life case series study conducted on consecutive diabetic macular edema patients who underwent treatment with one or more dexamethasone implant injections and were followed up for a minimum of 12 months. Subjects were divided into three groups: I-naïve patients, II-previously treated eyes that received three intravitreal antivascular endothelial growth factor inhibitors injections before the study (early switch), and III-previously treated eyes that received >3 intravitreal antivascular endothelial growth factor inhibitors injections before the study (late switch). Primary endpoints were best-corrected visual acuity and central retinal thickness at month 12. RESULTS: A total of 129 eyes (21 naïve and 108 previously treated, Group II: 32 and Group III: 76) were included. At month 12, best-corrected visual acuity significantly improved from 0.27 ± 0.23 and 0.31 ± 0.22 at baseline to 0.36 ± 0.25 and 0.37 ± 0.23 at month 12 in naïve and previously treated eyes, respectively, and p = 0.0063 and 0.0060, respectively. Central retinal thickness, in naïve and previously treated eyes, was significantly reduced from 483.0 ± 143.4 and 431.3 ± 115.5 µm, at baseline, to 278.8 ± 72.1 and 269.3 ± 66.2 µm, at month 12, respectively, and p < 0.0001 each, respectively. Best-corrected visual acuity improvement was significantly greater in both absolute and percentage values, p = 0.0393 and 0.0118, respectively, in Group II than in Group III. CONCLUSION: In eyes with insufficient response to antivascular endothelial growth factor inhibitors, switching to dexamethasone at the time to 3-monthly antivascular endothelial growth factor inhibitors injections provided better functional outcomes than those that received >3 antivascular endothelial growth factor inhibitors injections.

Treatment of Experimental Choroidal Neovascularization via RUNX1 Inhibition.

Choroidal neovascularization (CNV) is a prevalent cause of vision loss in patients with age-related macular degeneration. Runt-related transcription factor 1 (RUNX1) has been identified as an important mediator of aberrant retinal angiogenesis in proliferative diabetic retinopathy and its modulation has proven to be effective in curbing pathologic angiogenesis in experimental oxygen-induced retinopathy. However, its role in CNV remains to be elucidated. This study demonstrates RUNX1 expression in critical cell types involved in a laser-induced model of CNV in mice. Furthermore, the preclinical efficacy of Ro5-3335, a small molecule inhibitor of RUNX1, in experimental CNV is reported. RUNX1 inhibitor Ro5-3335, aflibercept-an FDA-approved vascular endothelial growth factor (VEGF) inhibitor, or a combination of both, were administered by intravitreal injection immediately after laser injury. The CNV area of choroidal flatmounts was evaluated by immunostaining with isolectin B4, and vascular permeability was analyzed by fluorescein angiography. A single intravitreal injection of Ro5-3335 significantly decreased the CNV area 7 days after laser injury, and when combined with aflibercept, reduced vascular leakage more effectively than aflibercept alone. These data suggest that RUNX1 inhibition alone or in combination with anti-VEGF drugs may be a new therapy upon further clinical validation for patients with neovascular age-related macular degeneration.

Topical delivery of a small molecule RUNX1 transcription factor inhibitor for the treatment of proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is the leading cause of retinal detachment surgery failure. Despite significant advances in vitreoretinal surgery, it still remains without an effective prophylactic or therapeutic medical treatment. After ocular injury or retinal detachment, misplaced retinal cells undergo epithelial to mesenchymal transition (EMT) to form contractile membranes within the eye. We identified Runt-related transcription factor 1 (RUNX1) as a gene highly expressed in surgically-removed human PVR specimens. RUNX1 upregulation was a hallmark of EMT in primary cultures derived from human PVR membranes (C-PVR). The inhibition of RUNX1 reduced proliferation of human C-PVR cells in vitro, and curbed growth of freshly isolated human PVR membranes in an explant assay. We formulated Ro5-3335, a lipophilic small molecule RUNX1 inhibitor, into a nanoemulsion that when administered topically curbed the progression of disease in a novel rabbit model of mild PVR developed using C-PVR cells. Mass spectrometry analysis detected 2.67 ng/mL of Ro5-3335 within the vitreous cavity after treatment. This work shows a critical role for RUNX1 in PVR and supports the feasibility of targeting RUNX1 within the eye for the treatment of an EMT-mediated condition using a topical ophthalmic agent.

Bimonthly, treat-and-extend and as-needed ranibizumab in naïve neovascular age-related macular degeneration patients: 12-month outcomes of a randomized study.

PURPOSE: To assess the noninferiority of the treat-and-extend (T&E) and fixed bimonthly regimens of 0.5 mg intravitreal ranibizumab as compared with the pro re nata (PRN) in naïve patients with neovascular age-related macular degeneration (nAMD). METHODS: Phase IV, randomized, 12-month, multicentre trial. Patients aged ≥50 years with nAMD and visual impairment [best-corrected visual acuity (BCVA) between 23 and 78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters] were eligible. Patients (one eye per patient) were randomized to bimonthly, n = 103, T&E, n = 99 or PRN, n = 104. Noninferiority was established at five letters ETDRS. RESULTS: The mean (95% CI) difference in BCVA at 12 months was 7.2 (4.2-10.2), 6.4 (2.9-9.8), and 8.0 (51.1-11.0) in the bimonthly, T&E and PRN, respectively. The bimonthly or T&E regimens were not inferior to the PRN scheme. All regimens were associated with a significant reduction of central subfield thickness and volume. The mean (95% CI) number of injections in the bimonthly regimen (7.6, 7.5-7.7) was similar as compared with the PRN regimen (7.4, 6.7-8.0) (p = 0.159) but lower than in the T&E regimen (9.3, 8.9-9.7) (p < 0.001). CONCLUSION: At 12 months, bimonthly and T&E ranibizumab were noninferior to PRN in naïve nAMD.

Early and intermediate age-related macular degeneration: update and clinical review.

Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice.

ACUTE RETINAL DAMAGE AFTER USING A TOXIC PERFLUORO-OCTANE FOR VITREO-RETINAL SURGERY.

PURPOSE: To describe a series of retinal acute toxicity cases with severe visual loss after intraocular use of a toxic perfluoro-octane (PFO). The clinical presentation is described, and the likely causes are analyzed. New biological methods for testing safety of intraocular medical devices are proposed. METHODS: Information regarding a series of eyes suffering acute severe events after intraocular use of a toxic PFO was analyzed. Four types of spectroscopy, nuclear magnetic resonance, and chromatography were used to identify the potential PFO contaminants. Cultures of human retinal pigment epithelial cells (ARPE-19) and porcine neuroretina were used to quantify the toxicity of the suspect PFO lots. RESULTS: Of 117 cases of intraocular toxicity, 96 were considered clearly related to the use of PFO. Fifty-three cases had no light perception, and 97 had no measurable visual acuity. Retinal necrosis (n = 38) and vascular occlusion (n = 33) were the most characteristic findings. Two hydroxyl compounds, perfluorooctanoic acid and dodecafluoro-1-heptanol, and benzene derivatives were identified as the suspected toxic agents. While existing toxicity testing failed, we proposed new tests that demonstrated clear toxicity. CONCLUSION: Protocols to determine cytotoxicity of intraocular medical devices should be revised to assure safety. Acute toxic events should be reported to health authorities and scientific media.

Ranibizumab in monotherapy and combined with photodynamic therapy for retinal angiomatous proliferation.

PURPOSE: To compare the effects of intravitreal ranibizumab in monotherapy (group A) and combined with photodynamic therapy (PDT) with verteporfin (group B) in retinal angiomatous proliferation (RAP) treatment. METHODS: This was a multicentric, prospective, randomized clinical study conducted with parallel groups. The study eye in both groups received ranibizumab on days 1, 30, and 60 (loading dose); group B received PDT additionally on day 1. Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) testing and optical coherence tomography were performed monthly, and fluorescein angiography and indocyanine green angiography were performed quarterly. Retreatment criteria were leakage in fluorescein angiography or indocyanine green angiography, mean foveal thickness increase ≥100 µm, or VA decrease ≥5 letters. RESULTS: Twenty patients were recruited (ten patients in each group). Six eyes had previous treatment (three eyes in group A and three eyes in group B), so only 14 eyes were naïve. At 12-month follow-up, mean VA improved +1.5 letters in group A and +5.6 letters in group B (analysis of variance test; P>0.05). Two patients (20%) in both groups gained ≥15 letters (chi-square test; P>0.05). Mean changes in greatest linear dimension and in foveal thickness were not statistically significant between groups of treatment (analysis of variance test; P>0.05). Mean retreatments per patient were 1.8 (group A) and 0.9 (group B) (Mann-Whitney U-test; P>0.05). One patient died due to underlying disease not related to study medication. CONCLUSION: Intravitreal ranibizumab administered in monotherapy or combined with PDT was efficacious in terms of VA stabilization in patients with RAP.

En face mode of swept-source optical coherence tomography in circumscribed choroidal haemangioma.

PURPOSE: To describe the findings in circumscribed choroidal haemangioma (CCH) using en face swept-source optical coherence tomography (SS-OCT). METHODS: En face images were obtained employing DRI-1 Atlantis OCT (Topcon, Tokyo, Japan), using a three-dimensional volumetric scan of 12×9 mm. Images were obtained from the retinal pigment epithelium to 1000 µm in depth of the tumour. RESULTS: Twenty-two eyes from 22 patients with the clinical diagnosis of CCH were included. In 20 eyes (90.9%), a characteristic pattern was visualised in the en face image across the vascular tumour. A multilobular pattern, similar to a honeycomb, with hyporeflective, confluent, oval or round areas corresponding with the lumen of the tumour vascular spaces, and hyper-reflective zones, which may represent the vessels walls and connective tissue of the tumour. Ten eyes (45.4%) showed a hyper-reflective halo surrounding the tumour. Seventeen tumours (77.2%) showed small diameter vessels at the inner zone and larger vessels in the outer area. Twelve patients (54.5%) had previously received treatment (photodynamic therapy, transpupillary thermotherapy, dexamethasone intravitreal implant or brachytherapy with ruthenium-106). No differences were found between treated and untreated patients in any of the measured parameters. CONCLUSIONS: En face SS-OCT is a rapid, non-invasive, high-resolution, technology, which allows a complementary study to cross-sectional scans in CCH. A characteristic multilobular pattern, with a hyper-reflective halo surrounding the tumour, was found in en face SS-OCT images. No morphological differences were found between naïve patients and patients who received previous treatment.

Treatment of Exudative Age-related Macular Degeneration: Focus on Aflibercept.

A formulation of aflibercept for intravitreal injection (Eylea) is approved for the treatment of patients with exudative age-related macular degeneration (AMD). Aflibercept has a significantly higher affinity for Vascular endothelial growth factor (VEGF)-A compared with other monoclonal anti-VEGF antibodies. In addition to binding all VEGF-A isoforms, aflibercept also blocks other proangiogenic factors such as VEGF-B and placental growth factor. The VIEW 1 and 2 trials showed this drug achieves improved results in patients with exudative AMD similar to those obtained with monthly ranibizumab, using a bimonthly treatment regimen after a loading dose of three intravitreal injections, which translates to less use of healthcare resources. There is a subgroup of patients that present with persistent fluid after the loading dose that could benefit from monthly injections or personalized proactive treatment after the first year. In the second year of treatment, the Treat and Extend patterns can permit even more lengthening of the time between injections. More data are needed to confirm the optimal monitoring and retreatment dosing, to maintain long-term efficacy. Other preliminary data suggest that patients that do not respond to other anti-angiogenics and patients with special pathologies such as polypoidal choroidopathy or retinal angiomatous proliferation can improve upon switching to aflibercept. To date, the safety profile of aflibercept is excellent and is comparable to other anti-angiogenic treatments.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY FOR CHOROIDAL NEOVASCULARIZATION SECONDARY TO PATHOLOGIC MYOPIA: SIX YEARS OUTCOME.

PURPOSE: To report the visual outcome after 6-year follow-up in highly myopic eyes with choroidal neovascularization treated with anti-vascular endothelial growth factor drugs. METHODS: Retrospective, nonrandomized, multicenter, consecutive, and interventional case series. RESULTS: Seventy-eight patients were treated with intravitreal bevacizumab and 19 with ranibizumab. Mean age of the patients was 56.5 years (SD, 13.3). The average number of letters read was 56.7 (SD, 19.0) at baseline; 65.7 (SD, 18.4) at 12 months; 63.6 (SD, 20.6) at 24 months; 62.4 (SD, 21.4) at 36 months; 60.6 (SD, 22.0) at 48 months; 58.9 (SD, 22.9) at 60 months, and 58.4 (SD, 22.7) at 72 months (P < 0.01, between initial vs. 12, 24, and 36 months; P = 0.07, 0.3, and 0.5 between initial vs. 48, 60, and 72 months, respectively; Student's t-test paired data). The mean total number of intravitreal injections was 3.3 (SD, 2.3; range, 1-9). CONCLUSION: Bevacizumab and ranibizumab are effective therapies and show similar clinical effects in myopic eyes with choroidal neovascularization. Visual acuity gain is maintained at a 3-year follow-up. The improvement is no longer statistically significant at Years 4, 5, and 6.

BAX and BCL-2 polymorphisms, as predictors of proliferative vitreoretinopathy development in patients suffering retinal detachment: the Retina 4 project.

PURPOSE: To compare the distribution of BCL-2 -938C>A (rs2279115) and BAX -248G>A (rs4645878) genotypes among European subjects undergoing rhegmatogenous retinal detachment (RRD) surgery in relation to the further development of proliferative vitreoretinopathy (PVR). METHODS: A case-control gene association study, as a part of Retina 4 project, was designed. rs2279115 and rs4645878 polymorphisms were analysed in 555 samples from patients with RRD (134 with PVR secondary to surgery). Proportions of genotypes and AA homozygous groups of BCL-2 and BAX polymorphisms between subsamples were analysed in two phases. Genotypic and allelic frequencies were compared in global sample and in subsamples. RESULTS: BAX: Differences were observed in the genotype frequencies and in AA carriers between controls and cases in the global series. The odds ratio (OR) of A carriers in the global sample was 1.7 (95% CI: 1.23-2.51). Proportions of genotypes in Spain + Portugal were significant different. The OR of A carriers from Spain and Portugal was 1.8 (95% CI: 1.11-2.95). BCL-2: No significant differences were observed in genotype frequencies. However, proportions of genotypes in Spain + Portugal were significant. A protective effect (OR: 0.6 95% CI: 0.43-0.96) was found in A carriers from Spain and Portugal. CONCLUSIONS: Results suggest that A allele of rs4645878 could be a biomarker of high risk of developing PVR in patients undergoing RD surgery. The possible role of BCL-2 (inhibitor of necroptosis pathway) as a possible new target in PVR prophylaxis should be investigated.

LONG-TERM OUTCOMES OF 23-GAUGE PARS PLANA VITRECTOMY WITH INTERNAL LIMITING MEMBRANE PEELING AND GAS TAMPONADE FOR MYOPIC TRACTION MACULOPATHY: A Prospective Study.

PURPOSE: To investigate the long-term safety and efficacy of microincisional 23-gauge pars plana vitrectomy with internal limiting membrane (ILM) peeling and gas tamponade in the treatment of myopic traction maculopathy. METHODS: A prospective nonrandomized multicenter study was designed. Patients with myopic traction maculopathy without macular hole and retinal detachment were included in the study between January 2009 and May 2012. All patients underwent microincisional 23-gauge pars plana vitrectomy with ILM peeling and 12% C3F8 gas tamponade. In all cases, brilliant blue G staining of the ILM was performed. All patients were prospectively evaluated. The evolution of best-corrected visual acuity (BCVA) and macular thickness were recorded. RESULTS: Myopic traction maculopathy resolved in 28 of the 30 patients (93%) included. Mean follow-up was 33.8 ± 13 months (range, 24-60 months). Mean time of myopic traction maculopathy resolution after surgery was 2.65 ± 1.4 months. At 1 month after surgery, one patient developed a macular hole and another one a rhegmatogenous retinal detachment. After 2 years, another patient developed a retinal detachment. Statistically significant improvements in macular thickness compared with baseline were found at all follow-up visits (P < 0.001, Student's t-test). At final visit, BCVA improved significantly compared with baseline (P = 0.044, Wilcoxon's test). However, a statistically significant improvement in visual acuity was achieved only in eyes with a preoperative Snellen visual acuity ≥ 20/63 (P = 0.027). In contrast, the final BCVA of eyes with worse preoperative visual acuity (<20/63) did not improve significantly (P = 0.41, Wilcoxon's test). CONCLUSION: Microincisional 23-gauge pars plana vitrectomy with ILM peeling and gas tamponade is effective in the treatment of myopic traction maculopathy, with low postoperative complications. Globally, both BCVA and macular thickness improved significantly during the follow-up period. However, greater visual acuity improvements were only seen in eyes with preoperative BCVA equal to or better than 20/63 Snellen equivalent. Some concerns remain about the risk of macular hole formation after ILM peeling. Further studies are necessary to investigate this issue.

The T309G MDM2 gene polymorphism is a novel risk factor for proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1-53.0)/(22.6-32.9), Portugal (39.0-74.4)/(21.4-38.9), Netherlands (40.6-66.3)/(25.3-38.8) and UK (37.5-62.4)/(23.3-34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2-12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8-19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR.