Resultados a largo plazo del tratamiento de la degeneración macular asociada a la edad neovascular mediante fármacos antiangiogénicos: revisión de la bibliografía / Long-term results of treatment of neovascular age-related macular degeneration using antiangiogenic drugs: A review of the literature

La degeneración macular asociada a la edad (DMAE) constituye una de las principales causas de la pérdida de agudeza visual (AV) en los mayores de 50 años en el mundo, siendo la DMAE neovascular (DMAEn) la causante del 80% de los casos de pérdida de visión severa debido a esta enfermedad. Hace ya más de una década que se emplean los fármacos antifactor de crecimiento del endotelio vascular (anti-VEGF) para el tratamiento de esta enfermedad, cambiando drásticamente el pronóstico visual de estos pacientes. Sin embargo, los primeros estudios de los que se disponían datos de los resultados eran a corto plazo. En la actualidad existen ya diferentes series publicadas de los resultados de la DMAE a largo plazo tras el tratamiento con anti-VEGF, siendo el objetivo de la presente revisión sintetizar dichos resultados. El seguimiento medio de los estudios incluidos fue de 8,2 años (rango: 5-12 años). La AV inicial media fue 55,3 letras del Early Treatment Diabetic Retinopathy Study (ETDRS) (rango: 45,6-65) siendo la AV final media 50,1 letras (rango: 33,0-64,3), existiendo una pérdida media de 5,2 letras. Al final del seguimiento un 29,4% de los pacientes mantuvieron una AV>70 letras. El 67,9% de los pacientes se mantuvo estable al final del seguimiento (<15 letras de pérdida), existiendo una pérdida severa (≥15 letras) del 30,1%. La fibrosis y la atrofia fueron las principales causas de pérdida de AV a largo plazo, presentándose al final del seguimiento en un 52,5% y un 60,5%, respectivamente.(AU)

Age-related macular degeneration (AMD) is one of the main causes of visual acuity (VA) loss in people over 50 years of age worldwide, with neovascular AMD (nAMD) accounting for 80% of cases of severe vision loss due to this disease. Anti-vascular endothelial growth factor (anti-VEGF) drugs have been used for the treatment of this disease for more than a decade, changing drastically the visual prognosis of these patients. However, initial studies reporting data on outcomes were short term. Currently, there are different series published on the long-term results of AMD after treatment with anti-VEGF, and the aim of this review is to synthesize these results. The mean follow-up of the included studies was 8.2 years (range 5-12 years). The mean initial VA was 55.3 letters in the Early Treatment Diabetic Retinopathy Study (ETDRS) (range 45.6-65) and the mean final VA was 50.1 letters (range 33.0-64.3), with a mean loss of 5.2 letters. At the end of follow-up, 29.4% of the patients maintained a VA>70 letters. The 67.9% of patients remained stable at the end of follow-up (<15 letter loss), with a severe loss (≥15 letters) of 30.1%. Fibrosis and atrophy were the main causes of long-term VA loss, occurring at the end of follow-up in 52.5% and 60.5%, respectively.(AU)

Subthreshold micropulse laser therapy for early postoperative macular thickening following surgical removal of epiretinal membrane.

BACKGROUND: This study aimed to investigate the functional and anatomical outcomes of subthreshold micropulse laser (SMPL) therapy in eyes with early postoperative macular thickening after idiopathic epiretinal membrane (iERM) removal. METHODS: This was a prospective and interventional study. Forty-eight eyes from 48 patients with macular edema at 1 month after iERM removal were randomly divided into two groups. Patients in the SMPL group (n = 24) received SMPL therapy while no special intervention was used for the observation group (n = 24). Baseline demographic data and clinical findings before and at 1 and 3 months after SMPL treatment or observation, including best-corrected visual acuity (BCVA) and the changes in central subfield thickness (CST) and average macular thickness (AMT), were analyzed. RESULTS: An improvement in BCVA with a decrease in CST and AMT from baseline to the 3-month follow-ups were observed in both SMPL and observation groups. No significant difference in BCVA was observed between the SMPL group and observation group either in the 1-month (0.26 [0.15, 0.52] vs. 0.26 [0.15, 0.39], P = 0.852) or the 3-month (0.15 [0.10, 0.30] vs. 0.23 [0.15, 0.30], P = 0.329) follow-up. There was a greater reduction in CST in the SMPL group versus observation group between baseline and the 3-month follow-up (-77.8 ± 72.3 µm vs. -45.0 ± 46.9 µm, P = 0.049). The alteration in AMT did not differ between the two groups in either 1-month (-16.5 ± 20.1 µm vs. -19.7 ± 16.3 µm, P = 0.547) or 3-month (-36.9 ± 26.9 µm vs. -34.0 ± 20.1 µm, P = 0.678) follow-up. CONCLUSIONS: SMPL therapy led to a significant decrease in CST at the 3-month follow-up while did not significantly improve the visual acuity in patients with postoperative macular thickening following iERM surgery. TRIAL REGISTRATION: The study was registered on Aug 27, 2020 (Trial Registration Number: ChiCTR 2000037227).

Epiretinal Membrane Surgery in Eyes with Glaucoma: Visual Outcomes and Clinical Significance of Inner Microcystoid Changes.

OBJECTIVE: To investigate visual acuity (VA) outcomes and OCT-based biomarkers of vision outcomes in eyes with glaucoma undergoing pars plana vitrectomy (PPV) for idiopathic epiretinal membrane (ERM). DESIGN: Retrospective, consecutive case-control series. A previously described ERM grading scale was utilized for OCT analysis. SUBJECTS: Eyes with glaucoma undergoing PPV for idiopathic ERM. INTERVENTION: PPV with membrane peel (MP) surgery. MAIN OUTCOME MEASURES: The primary outcome was VA at postoperative month 6. Outcomes were compared to a contemporary, matched control group of eyes without concurrent glaucoma undergoing PPV for idiopathic ERM. RESULTS: A total of 103 eyes from 103 patients with ERM and glaucoma were followed for a mean (± standard deviation) of 656 (± 421) days after PPV with MP surgery. Glaucoma was classified as open angle in 98 (95.1%) eyes and closed angle in 5 (4.9%) eyes. Visual acuity improved from 0.72 ± 0.48 (20/105) to 0.55 ± 0.51 (20/71) at 6 months and to 0.50 ± 0.56 (20/63) at final follow-up (P < 0.001 for both the time points). Eyes with preoperative inner microcystoid changes (n = 59; 57.3%) had significantly worse preoperative VA, postoperative VA at month 6, and final VA compared to eyes without inner microcystoid changes (P = 0.028, 0.004, and 0.007, respectively). Eyes were then compared to a matched control group of 139 eyes without glaucoma. Eyes with ERM and glaucoma had a higher rate of microcystic changes both before surgery (P < 0.001) and at postoperative month 6 (P < 0.001), and had a worse VA at 6 months (P = 0.03) and final follow-up (P = 0.04) compared to control eyes without glaucoma. Advanced disc cupping was the only factor independently correlated with worse 6-month (P = 0.01) and final (P = 0.007) VA in multivariate analysis. CONCLUSIONS: Preoperative inner microcystoid changes on OCT were present in over half of eyes with ERM and concurrent glaucoma, and may be a poor prognostic OCT biomarker. Eyes with ERM and concurrent glaucoma experienced worse vision outcomes compared to eyes with ERM alone, particularly those with advanced disc cupping.

Persistent macular holes - what is the best strategy for revision?

PURPOSE: This study aims to analyze the success rate and functional outcome after revision surgery of persistent idiopathic full-thickness macular holes in a large patient cohort and to identify the optimal tamponade strategy and the value of new adjunctive manipulation techniques for persistent macular hole (pMH) closure. METHODS: Retrospective, comparative, non-consecutive case series of all revisional surgeries for idiopathic pMH between 2011 and 2019 at the Eye Clinic Sulzbach were identified. Of 1163 idiopathic MH surgeries, 74 eyes of 74 patients had pMH. Of those, group 1 (n = 38) had vitrectomy with tamponade alone (20% sulfur hexafluoride gas, 15% hexafluoroethane gas, silicone oil 5000, Densiron®), while group 2 (n = 36) included tamponade with adjuvant manipulation (internal limiting membrane (ILM) translocation, subretinal fluid injection, epiretinal amniotic membrane, free retina graft, or autologous blood). Main statistical outcomes were anatomic closure rate, visual acuity (VA), minimum linear diameter (MLD), and base diameter (BD). RESULTS: Overall total anatomical success rate was 81.1% and mean VA improved 3.5 lines from LogMAR 1.03 ± 0.30 to 0.68 ± 0.38 (p < .001). Preoperative MLD or BD had no effect on total anatomic success (p = 0.074, p = 0.134, respectively). When comparing the two groups, slightly better anatomic success rates were achieved in group 1 (84.2%) compared to that in group 2 (77.8%) (p = 0.68). Final VA in group 1 (LogMAR 0.67 ± 0.39) outperformed group 2 (LogMAR 0.86 ± 0.38) (p = 0.03). CONCLUSIONS: Revisional surgery for persistent idiopathic MH with tamponade alone had comparable anatomical closure but better VA outcomes, compared to tamponade with adjuvant manipulation.

Vitreous composition modification after transpalpebral electrical stimulation of the eye: Biochemical analysis.

Electrical stimulation (ES) of the eye represents a therapeutic approach in various clinical applications ranging from retinal dystrophies, age-related macular degeneration, retinal artery occlusion and nonarteritic ischemic optic neuropathy. In clinical practice, ES of the eye is mainly performed with a transcorneal or transpalpebral approach. These procedures are non-invasive and well-tolerated by the patients, reporting only minimal and transient adverse events, while serious adverse effects were not observed. Despite the growing literature on animal models, only clinical parameters have been investigated in humans and few data are available about biochemical changes induced by ES of the eye. The purpose of this study is to investigate the possible mechanism that regulates the beneficial effects of ES on retinal cells function and survival in humans. 28 patients undergoing pars plana vitrectomy (PPV) for idiopathic epiretinal membrane (iERM) were randomly divided in two groups: 13 patients were treated with transpalpebral ES before surgery and 15 underwent surgery with no prior treatment. Vitreous samples were collected for biochemical analysis during PPV. ES treatment leads to a reduction in the vitreous expression of both proinflammatory cytokines, namely IL-6 and IL-8, and proinflammatory lipid mediators, such as lysophosphatidylcholine. Indeed, we observed a 70% decrease of lysophosphatidylcholine 18:0, which has been proven to exert the greatest proinflammatory activities among the lysophosphatidylcholine class. The content of triglycerides is also affected and significantly decreased following ES application. The vitreous composition of patients undergoing PPV for iERM displays significant changes following ES treatment. Proinflammatory cytokines and bioactive lipid mediators expression decreases, suggesting an overall anti-inflammatory potential of ES. The investigation of the mechanism by which this treatment alters the retinal neurons leading to good outcomes is essential for supporting ES therapeutic application in various types of retinal diseases.

Color and cellular selectivity of retinal ganglion cell subtypes through frequency modulation of electrical stimulation.

Epiretinal prostheses aim at electrically stimulating the inner most surviving retinal cells-retinal ganglion cells (RGCs)-to restore partial sight to the blind. Recent tests in patients with epiretinal implants have revealed that electrical stimulation of the retina results in the percept of color of the elicited phosphenes, which depends on the frequency of stimulation. This paper presents computational results that are predictive of this finding and further support our understanding of the mechanisms of color encoding in electrical stimulation of retina, which could prove pivotal for the design of advanced retinal prosthetics that elicit both percept and color. This provides, for the first time, a directly applicable "amplitude-frequency" stimulation strategy to "encode color" in future retinal prosthetics through a predictive computational tool to selectively target small bistratified cells, which have been shown to contribute to "blue-yellow" color opponency in the retinal circuitry. The presented results are validated with experimental data reported in the literature and correlated with findings in blind patients with a retinal prosthetic implant collected by our group.

Anatomical and functional outcomes one year after vitrectomy and retinal massage for large macular holes.

Purpose: The aim of this study was to report results of macular hole closure, visual benefit and longitudinal changes in foveal architecture over 1 year following macular hole surgery with retinal massage. Methods: Records of patients with full thickness macular hole (FTMH) with minimum basal diameter of 550 µ who underwent vitrectomy, internal limiting membrane (ILM) peeling and retinal massage were drawn up. Retinal massage was performed after dye assisted ILM peeling, using a 27G flute needle with a long and soft silicone tip under air in a centripetal direction around the FTMH. At the end, 10% C3F8 gas was used as tamponade. The foveal contour at 1 year follow up was recorded based on its cross sectional appearance on OCT and was classified into U, V and irregular types of closure as previously described. Results: Forty-one eyes of 41 patients with a mean age of 70.4 ± 6.9 years were included. The mean preoperative vision was 0.99 ± 0.07 logMAR and mean maximum basal diameter of the FTMH was 835 ± 208 µ. Macular hole closure was seen in all patients at 1-month follow up. The BCVA improved to 0.5 ± 0.1 log MAR at 6 months (P < 0.001) and then stabilized. The U shaped closure was the commonest pattern (n = 22, 54%), followed by V-shaped closure (n = 16, 39%) while irregular closure was seen in 3 eyes (7%). Conclusion: Retinal massage after ILM peeling is a very simple, and as yet under-utilized manoeuvre that may improve hole closure rates and lead to potentially greater improvement in vision compared to existing techniques for large holes.

Relationship between nerve fiber layer defect and the presence of epiretinal membrane in a Japanese population: The JPHC-NEXT Eye Study.

The study subjects were residents of Chikusei city, Japan, aged 40 years or older who attended annual health check-up programs and participated in the JPHC-NEXT Eye Study which performed non-mydriatic fundus photography of both eyes. The relationship of glaucomatous fundus changes such as optic disc cupping (cup to disc ratio ≥ 0.7) and retinal nerve fiber layer defect (NFLD) with the presence of epiretinal membrane (ERM) were examined cross-sectionally. A total of 1990 persons gave consent to participate in this study in 2013. The overall prevalence of ERM was 12.9%. Of these, 1755 had fundus photographs of sufficient quality and no history of intraocular surgery (mean age: 62.3 ± 10.0 years). After adjusting for age, sex and refractive error, NFLD was positively associated with the presence of ERM (odds ratio [OR]: 2.48; 95% confidence interval [CI]: 1.24, 4.96; P = 0.010), but optic disc cupping was not (OR: 1.33; CI: 0.71, 2.48; P = 0.37). The results did not necessarily suggest an association between glaucoma and ERM, but indicated an association between NFLD and ERM.

Incidence and impact factors of intraoperative loss of light perception under sub-Tenon's anesthesia in patients with macular diseases.

PURPOSE: To investigate the incidence and impact factors of intraoperative loss of light perception (LP) under sub-Tenon's anesthesia in patients with macular diseases. METHODS: Eighty-five consecutive patients received standard phacoemulsification combined pars plana vitrectomy (PPV) under sub-Tenon's anesthesia. At several checkpoints during the surgery (the end of phacoemulsification, the end of vitrectomy, and the end of surgery), participants were interviewed about whether they had LP or not after removing the influence of contralateral eye and the photo-bleaching effect. In patients treated with retinal photocoagulation, visual experience on laser flashes was evaluated. RESULTS: Under routine draping, no patients reported loss of LP at all the checkpoints. When the contralateral eye was tightly covered, the rates of LP loss were 84.7%, 97.6%, and 87.1% at the end of phacoemulsification, the end of vitrectomy, and the end of surgery, respectively. When the photo-bleaching effect was also removed, the rates of LP loss were 61.2%, 82.4%, and 56.5% at each checkpoint, respectively, and there were 87.1% (74/85) of patients reporting visual loss in at least one checkpoint. In addition, 76.9% (50/65) of patients could not feel laser flashes during retinal photocoagulation. CONCLUSION: Intraoperative loss of LP under sub-Tenon's anesthesia was a relatively common and reversible event. The conduction block of optic nerve by anesthetic mainly contributed to the visual loss during surgery. Photo-bleaching effect also has some effect on the LP evaluation. Surgeons need to inform and counsel the patients about the intraoperative loss of LP, to prevent any sudden panic attacks in them.

Cross-Sectional Imaging Analysis of Epiretinal Membrane Involvement in Unilateral Open-Angle Glaucoma Severity.

Purpose: To determine the relevance of epiretinal membranes (ERMs) in primary open-angle glaucoma (POAG) and potential risk for glaucoma severity. Methods: Sixty eyes of 30 patients with POAG who had a unilateral ERM were analyzed; 60 nonglaucomatous eyes of 30 patients with a unilateral ERM also were recruited in this institutional cross-sectional study. Patients underwent swept-source (SS) optical coherence tomography (OCT) imaging and visual field testing. Intraindividual differences in the SS-OCT retinal nerve fiber layer (RNFL) disc cupping area measurements and visual field outcomes were analyzed in the two groups. Results: In patients with POAG, the mean circumpapillary RNFL thickness in the eyes with an ERM was 75.6 ± 16.5 µm superiorly and 71.8 ± 26.0 inferiorly compared with the fellow eyes without an ERM (87.2 ± 23.6 µm, P = 0.0061 and 81.3 ± 27.7 µm, P = 0.034, respectively). The areas of disc cupping and cup-to-disc ratio seen on OCT horizontal and vertical B-scans were larger in eyes with an ERM than in the fellow eyes without ERM (P = 0.0004 and P = 0.0011, respectively). The average mean deviations were -11.6 ± 7.5 dB in the ERM group and -8.19 ± 6.4 dB in the group with no ERM (P = 0.029). Eyes with an ERM received more antiglaucoma eye drops (P = 0.018). Those differences were not seen between eyes with an ERM or fellow eyes in patients without glaucoma. Conclusions: The presence of an ERM can be a potential risk factor for unilateral severity in eyes with POAG.

Actualización sobre el manejo del tumor vasoproliferativo / Update on the management of vasoproliferative tumour

CASO CLÍNICO: Presentamos el caso de una paciente de 19 años con un tumor vasoproliferativo, en cuya evolución presentó una membrana epirretiniana, edema macular, hemovítreo y desprendimiento de retina exudativo. Se trató con 3 inyecciones intravítreas de bevacizumab, implante intravítreo de dexametasona, tocilizumab y 2 sesiones de crioterapia. DISCUSIÓN: Las opciones terapéuticas son: observación en los de menor tamaño, periféricos y sin amenaza para la visión. Si se necesita tratamiento, fotocoagulación con láser, crioterapia transconjuntival, inyecciones intravítreas de bevacizumab, termoterapia transpupilar, terapia fotodinámica, placas de radioterapia y cirugía son diferentes opciones disponibles. Recientemente se ha descrito que el tocilizumab y los implantes intravítreos de dexametasona pueden ser beneficiosos

CASE REPORT: Here we report a 19-year-old female patient who presented a vasoproliferative tumour. It caused complications, such as epiretinal membrane, macular oedema, vitreous haemorrhage, and exudative retinal detachment. The patient was treated with 3 injections of intravitreal bevacizumab, an intravitreal dexamethasone implant, tocilizumab, and double freeze-thaw cryotherapy. DISCUSSION: Therapeutic options are: observation, if it is small, if it is a peripheral lesion, and if there seems to be no threat to vision. If it requires treatment, laser photocoagulation, intravitreal bevacizumab, trans-conjunctival cryotherapy, transpupillary thermotherapy, photodynamic therapy, brachytherapy plaques and surgery are the different options available. Recently, tocilizumab and intravitreal dexamethasone implants have been reported to be beneficial

Trends of Pars Plana Vitrectomy Rates in South Korea: A Nationwide Cohort Study

PURPOSE: To assess the trends in pars plana vitrectomy surgery rates and factors affecting rate change between 2002 and 2013 in South Korea. METHODS: Data from National Health Insurance Service-National Sample Cohort 2002–2013, which represents 1,025,340 samples with a sampling rate of 2.2% from the total eligible Korean population, was analyzed. RESULTS: A total of 3,816 vitrectomy procedures were performed (male, 2,010; female, 1,806) from 2002 to 2013. Annual rates of vitrectomy increased from 15.1 (in 2002) to 49.4 (in 2013) per 100,000 individuals, and this trend was prominent in those aged 60 years or older. As for the anesthetic method, vitrectomy under local anesthesia increased more prominently than vitrectomy under general anesthesia. The most common diagnoses associated with vitrectomy were diabetic retinopathy, retinal detachment, epiretinal membrane, and macular hole. CONCLUSIONS: The average annual rate of vitrectomy surgery was 31.5 per 100,000 between 2002 and 2013, and the rate has steadily increased.

Brilliant Blue G double staining enhances successful internal limiting membrane peeling with minimal adverse effect by low cellular permeability into live cells.

PURPOSE: Brilliant Blue G is used as a surgical adjuvant for retinal surgery. Although BBG double or multiple staining was reported, the effectiveness and safety of repeated staining is still elusive. To further examine the effectiveness and safety, we examined BBG in clinical cases in vivo, primary cell culture in vitro, and surgically resected specimen ex vivo. METHODS: A retrospective interventional case series with in vitro and ex vivo studies were performed. Vitrectomy was performed in 28 cases of epiretinal membrane with BBG single to multiple staining. The surgically resected membranes were stained by BBG with or without cellular fixation. Primary cell cultures were examined with BBG and live/death cell markers, such as Calcein AM and TUNEL. RESULTS: Single staining provided satisfactory staining in seven cases. Double or multiple staining substantially visualized internal limiting membrane (21 cases), especially the edges of remaining internal limiting membrane (11 cases). Adverse retinal staining was not noted and the final visual acuity showed no difference with multiple staining. The live cells barely stained with BBG, while some dead cells were stained. CONCLUSION: Brilliant Blue G multiple staining substantially enhanced the visualization of internal limiting membrane. The absence of abnormal staining supports the safety of repeated BBG staining.

Optical coherence tomography and histopathology of macular uveitis.

PURPOSE: Spectral-domain optical coherence tomography (SD-OCT) is a noninvasive technique that can provide high-resolution images of macular morphology. The purpose of this study was to examine the pathological mechanism of uveitis and compare the changes in the macula of uveitis patients and the histopathological features of experimentally induced uveitis in mice. METHODS: Macular OCT was performed on 78 eyes of 51 patients of the Eye Hospital of Shandong University of Traditional Chinese Medicine, China, with apparent uveitis changes. C57BL/6 mice were injected with interphotoreceptor retinoid-binding protein (IRBP)-specific T cells from naïve mice immunized with complete Freund adjuvant IRBP(1-20) to induce uveitis. The disease was monitored by indirect fundoscopy. The eyes of the mice with experimental autoimmune uveitis (EAU) were enucleated 18 days after injection and classified according to pathological characteristics. RESULTS: The characteristics of uveitis were classified into six categories. Macular edema was detected in 48 eyes (61.5%); macular epiretinal membrane in 22 eyes (28.2%); choroidal neovascularization and macular lamellar holes in 4 eyes (5.1%), respectively; macular atrophy in 10 eyes (12.8%); and serous neuroepithelium detachment in 22 eyes (28.2%). As in human patients, pathological examinations of mouse EAU showed inflammation, folds, and atrophy of the outer part of the neuroretina, choroidal neovascularization with hemorrhagic retinal detachment, serous neuroepithelium detachment, and epiretinal membrane formation. CONCLUSIONS: Macular OCT of uveitis patients can display different morphological characteristics. Mouse EAU can simulate human uveitis. The comparative analysis of macular OCT in human uveitis and transfer EAU histopathology changes could provide important information on the pathogenesis of human uveitis.