Real-world experience with brolucizumab in neovascular age-related macular degeneration over 2 years: the REBA extension study.

BACKGROUND: To determine long-term efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in the real-world setting. METHODS: Retrospective, observational, multicentric study and an extension of the REBA study (Real-world Experience with Brolucizumab in nAMD) to 24 months. The study entailed follow-up of 91 consecutive eyes (67 patients) with nAMD who received brolucizumab therapy and completed 24 months of follow-up. Both treatment-naïve and switch therapy patients were included. All relevant data were collected. The primary outcome measure was changed in best-corrected visual acuity (BCVA) over time. Secondary outcome measures included change in central subfield thickness (CST) and complications. RESULTS: The mean (SD) baseline BCVA was 48.4 (3.5) letters and 36.2 (7.1) letters in treatment-naïve group and switch therapy group, respectively. BCVA gain was + 9.2 (3.7) letters (p = 0.01) and + 7.7 (3.4) letters (p = 0.011), respectively. The change in mean (SD) CST has shown a significant decrease in retinal thickness in treatment-naïve group (from 432.5 (68.4) to 283.0 (51.3) µm; p = 0.018) and in switch therapy group (from 452.5 (40.5) to 271.0 (43.4) µm; p = 0.011) group. One switch patient developed vascular occlusion and another a macular hole after the fifth brolucizumab injection as reported in the primary study. Both patients recovered uneventfully. Three patients demonstrated reversible intraocular inflammation between months 10 and 24. CONCLUSION: Patients showed a significant anatomical and functional response to brolucizumab therapy in the real world, regardless of prior treatment status, until the end of the follow-up period. Overall, 5 significant untoward events were noted.

Retinal Microvascular Density and Perfusion during an Insulin-Induced Hypoglycemia Episode: A Warning Call.

Aim: To evaluate retinal vascular perfusion and density by optical coherence tomography angiography (OCTA) before, during, and after hypoglycemia in individuals with diabetes mellitus with or without diabetic retinopathy (DR). Methods: A focused clinical history was performed, followed by an ophthalmological examination to document retinopathy status. OCTA was performed at baseline, at hypoglycemia, and at glucose normalization. Eye tracking and eye alignment devices on the platform were used to obtain a macular thickness cube (512 × 128) and vascular perfusion and density protocols of 3 × 3 mm. Retinal vascular reactivity was analyzed with superficial plexus vascular perfusion and density protocols on OCTA. Results: Fifty-two participants encompassing 97 eyes fulfilled the eligibility criteria. Their mean age was 42.9 ± 15.1 years (range, 22 to 65), and 20 (38.2%) were men. We found a statistically significant difference in vascular perfusion and density when comparing all groups at baseline. The controls had higher vascular perfusion and density values than the cases. Vascular perfusion and density were significantly reduced in all groups during the hypoglycemia episode, except for vascular density in DR cases. Conclusion: Acute hypoglycemia significantly alters the retinal vascularity in DM patients with and without DR, suggesting that repeated episodes of acute hypoglycemia could exacerbate retinopathy in the long term.

Suprachoroidal silicone oil as an intraoperative complication during Pars Plana Vitrectomy: A case report.

INTRODUCTION AND IMPORTANCE: Complications related to silicone oil tamponade are frequent. There are reports of events related to silicone oil (SO) injection during Pars Plana Vitrectomy (PPV). This case presents the unexpected injection of SO in the suprachoroidal space. The proper management of this complication along with the preventive measures are discussed. CASE PRESENTATION: A 38-year-old male presented with a one-week history of decreased vision in his right eye (OD). His visual acuity was hand motion (HM). A late-onset retinal detachment recurrence with proliferative vitreoretinopathy (PVR) in his OD was diagnosed. Cataract surgery and PPV were scheduled. During PPV, a choroidal detachment (CD) secondary to the suprachoroidal injection of silicone oil (SO) was noted. Suprachoroidal SO was identified timely and was managed with external drainage through a posterior sclerotomy. CLINICAL DISCUSSION: Suprachoroidal silicone oil injection is a potential complication during PPV. For the management of this complication, the drainage of the silicone oil from the suprachoroidal space through a posterior sclerotomy may be considered as an option. This complication may be avoided by periodically checking the correct position of the infusion cannula during the PPV, by injecting the SO into the vitreous cavity under direct visualization and by using automated injection systems. CONCLUSION: Suprachoroidal silicone oil injection is an intraoperative complication that might be avoided by cross-checking the correct position of the infusion cannula and by injecting SO under direct visualization.

Postoperative Aspergillus Infection: A Case Series.

PURPOSE: To report the clinical findings, therapy and outcomes of pauci-symptomatic Aspergillus infection in 11 eyes of 11 patients who had recently undergone uneventful cataract surgery and IOL implantation in a single operating room on the same day. METHODS: Retrospective, observational study that looks at 11 patients who demonstrated Aspergillus infection after cataract surgery. All data were collected and intracameral samples sent for microscopic evaluation and culture. Additional swabs were sent from the operating room and operative consumables. RESULTS: A total of 11 eyes of 11 patients were included in the analysis and were followed for at least 12 months. All patients responded completely to local and systemic voriconazole therapy. The source of infection was noted to be air-conditioning vents. Eyes with manual small incision cataract surgery (11/17) had a higher propensity for infection. CONCLUSION: Pauci-symptomatic aspergillosis infection has been reported here following cataract surgery.

Spontaneous closure of an idiopathic macular hole after epiretinal membrane development.

Purpose: To report non-operative closure of an idiopathic full thickness macular hole (FTMH) spontaneous secondary to the development of a macular epiretinal membrane (ERM). Observations: A 68-year-old woman, with no relevant medical history, and a 6-month history of decreased visual acuity in her right eye was diagnosed to have an idiopathic FTMH. The patient refused surgery and the FTMH was followed-up for seven years. The spectral domain optical coherent tomography follow-up showed the evolution of the FTMH and its spontaneous closure after development of an ERM. In the presence of an ERM with vitreo-papillary detachment, it is possible that the centripetal forces involved helped bring together the edges of the macular hole resulting in a possible spontaneous closure. Additionally and separately, the presence of an ERM may act as scaffolding for Muller cell migration and consequent macular hole closure. Conclusions and importance: Development of an ERM was followed by non-operative FTMH closure in this specific case. It is important to note, that this is an extraordinary situation in which the patient had a favorable anatomical evolution despite having rejected conventional surgical intervention. Studies aimed at determining the mechanisms and situations in which these cases occur could provide answers that help us make more appropriate decisions. To our knowledge, the present case is the first in the literature to report a spontaneous closure of a FTMH secondary to the appearance and progression of a previously non-existent ERM.

Current Treatments and Innovations in Diabetic Retinopathy and Diabetic Macular Edema.

Diabetic retinopathy (DR) is one of the leading causes of blindness worldwide. Multiple treatment options have been used over time to attempt to modify the natural progression of the disease in both proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). These two retinal complications are the result of microvascular occlusions and vascular hyperpermeability and are considered one of the leading causes of irreversible blindness in patients of working age. It is now well demonstrated that PDR and DME are associated with increased levels of inflammatory and pro-angiogenic factors in the ocular compartment. To date, laser photocoagulation, vascular endothelial growth factor (VEGF) inhibitors, and corticosteroids have demonstrated efficacy in their treatment in large randomized controlled trials and in real-life observational studies. This manuscript aims to provide a comprehensive review of current treatments, including the main drugs used in diabetic pathologic manifestations, as well as new therapeutic alternatives, such as extended-release intraocular devices.

Relationship of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratio With Visual Acuity After Surgical Repair of Open Globe Injury.

Purpose: To assess the relationship and prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with poor final best-corrected visual acuity (BCVA) after surgical repair of open globe injuries (OGI) in adults. Design: Retrospective analysis of data from an ongoing prospective cohort of consecutive patients. Methods: In a tertiary university hospital, 197 eyes of 197 patients were included between 2013 and 2017. NLR and PLR were obtained from pre-operative blood tests to analyze its relationship with poor final BCVA. Results: Severe visual impairment (SVI) was defined as ≤20/200, and was observed in 96 (48.7%) patients after surgical repair of OGI. SVI patients had higher NLR (7.4 ± 6.6 vs. 4.0 ± 3.2, p < 0.001), and PLR (167 ± 92 vs. 139 ± 64; p = 0.021) than non-SVI. NLR ≥ 3.47 and PLR ≥ 112.2 were the best cut-off values for SVI, were univariate risk factors for SVI, and had sensitivity: 69.0, 71.4, and specificity: 63.6, 44.8, respectively. In multivariate analysis, only OTS, athalamia, and hyphema remained as risk factors. NLR had significant correlation with ocular trauma score (OTS) (r = -0.389, p < 0.001) and final BCVA (r = 0.345, p < 0.001). Limitations: Simultaneous trauma in other parts of the body that could influence the laboratory findings. Conclusion: Patients with SVI after a repaired OGI had increased pre-operative NLR and PLR levels. High NLR and PLR are risk factors for SVI in univariate analysis. It is confirmed that low OTS is a risk factor for SVI. High NLR and PLR could be used as a prognostic tool to identify patients at higher risk for SVI after repair of OGI.

Topical Triamcinolone Acetonide-Loaded Liposome Formulation Used as an Adjuvant to Intravitreal Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration.

Novel strategies have been developed to reduce or avoid intravitreal injections (IVTs) of the antiangiogenic (ranibizumab (RBZ)) and anti-inflammatory (triamcinolone acetonide (TA)) agents used to treat vitreoretinal diseases. One of the strategies includes liposomes. This study evaluated the safety and efficacy of a topical triamcinolone-loaded liposome formulation (TALF) as an adjuvant to intravitreal RBZ therapy in treatment- naïve patients with neovascular age-related macular degeneration (nAMD). Subjects were randomly assigned to the RBZ-TALF or the RBZ-pro re nata (RBZ-PRN) groups. Patients from the RBZ-TALF group were instructed to apply TALF for 12 months after a single dose of RBZ. Patients from the RBZ-PRN group received three monthly RBZ-IVTs. Retreatment with RBZ was considered in the case of nAMD reactivation. Regarding safety, non-ocular abnormalities were observed during TALF therapy. Concerning efficacy, non-significant differences were identified in terms of visual acuity or central foveal thickness when the RBZ-PRN and RBZ-TALF groups were compared. It is worth noting that the average number of RBZ injections was significantly lower in the RBZ-TALF group (2.5 ± 1.4 vs. 6.1 ± 1.3 IVTs; p = 0.0004). Therefore, TALF used as an adjuvant to RBZ reduces the need for RBZ-IVT retreatment with optimal visual and anatomic results.

Real-World Experience with Brolucizumab in Wet Age-Related Macular Degeneration: The REBA Study.

The aim of the present study was to determine the efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (AMD) in the real-world setting. The REBA study (real-world experience with brolucizumab in wet AMD) was a retrospective, observational, multicentric study that included 78 consecutive patients (105 eyes), with neovascular AMD, who received brolucizumab therapy. Both treatment-naive and switch-therapy patients were included. Switch therapy was based either on fluid recurrence, fluid recalcitrance, or inability to extend beyond q4/q6. All relevant data were collected. The primary outcome measure was change in best-corrected visual acuity (BCVA) over time. Secondary outcome measures included determination of change in central subfield thickness (CST) and complications. The mean baseline BCVA was 49.4 ± 5.4 letters and 40 ± 3.2 letters, and corresponding mean BCVA gain was +11.9 ± 3.9 letters (p = 0.011) and +10.4 ± 4.8 letters (p = 0.014) in the treatment-naive and switch-therapy groups, respectively. The change in CST was significantly decreased in the treatment-naive (p = 0.021) and the switch-therapy (p = 0.013) groups. The mean follow-up was 10.4 months in both groups. One patient in the switch-therapy group developed vascular occlusion and another a macular hole after the fifth brolucizumab injection. Both patients recovered uneventfully. In conclusion, patients showed a very good anatomical and functional response to brolucizumab therapy in the real world, regardless of prior treatment status, until the end of the follow-up period. Two significant untoward events were noted.

ENDOGENOUS ENDOPHTHALMITIS IN THE SETTING OF COVID-19 INFECTION: A Case Series.

PURPOSE: To describe endogenous endophthalmitis in the setting of COVID-19 pneumonia. METHODS: Patients recovering from COVID-19 pneumonia who presented to our department with any or all of the following complaints: pain, watering, redness, and decreased vision were identified. All relevant data were collected for analysis. RESULTS: Three patients with endogenous endophthalmitis were identified. All patients had been treated for COVID-19 pneumonia and therefore had received remdesivir and systemic steroids; 2 of the 3 patients received tocilizumab. All patients received vitreous biopsy, vitrectomy, and intraocular antibiotic injection. Patient 1 demonstrated Klebsiella pneumoniae in blood culture, K. pneumoniae and Escherichia coli in urine culture, and K. pneumoniae in vitreous fluid, whereas Patients 2 and 3 demonstrated Stenotrophomonas maltophilia and methicillin-resistant Staphylococcus aureus in the blood and nasopharyngeal culture, respectively. Correspondingly, the same organism was cultured from vitreous in Patients 2 and 3. The visual acuity at the last follow-up in Patients 1 to 3 was 20/100, 20/80, and 20/40, respectively. The probable source of infection was identified in each as renal calculi, dental caries, and the pharynx, respectively. Real-time polymerase chain reaction demonstrated the presence of Severe Acute Respiratory Syndrome Coronavirus 2 in the vitreous fluid of Patient 1. CONCLUSION: We report good outcomes of early intervention for endogenous endophthalmitis in the setting of COVID-19 infection. We also document the presence of SARS-CoV-2 in vitreous.

SPONTANEOUS CLOSURE OF SIMULTANEOUS IDIOPATHIC MACULAR HOLES DOCUMENTED BY SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To report a case of spontaneous closure of simultaneous full-thickness macular hole. METHODS: Case report and literature review. RESULTS: A 67-year-old woman with small-diameter simultaneous macular holes was observed for a period of 5 months, and progression was documented with spectral-domain optical coherence tomography. Closure of right full-thickness macular hole was evidenced by 1 month and left full-thickness macular hole by 5 months. CONCLUSION: This case demonstrates possible spontaneous resolution of a condition that is usually treated surgically. A period of observation with serial imaging studies may be advised in cases of small macular holes.

Closure of stage 2 macular hole with a low-dose intravitreal injection of perfluoropropane.

BACKGROUND: Idiopathic macular holes (IMH) are common and affect central vision. We demonstrate the effectiveness of 0.2 ml intravitreal perfluoropropane (C3F8) in Stage-2 IMH. CASE: A 61-year-old woman presented with blurred vision OD. Best-corrected visual acuity (BCVA) was 20/125 OD and 20/20 OS. Biomicroscopy of OD evidenced a Stage-2 IMH. Intravitreal C3F8 was injected and postural measures prescribed. Optical coherence tomography 1 week after revealed posterior vitreous detachment and vitreomacular traction resolution. Full anatomical and functional recovery was achieved at week 4 and remained stable during a 6-month follow-up (BCVA 20/20 OD). CONCLUSION: Intravitreal C3F8 as initial therapy for Stage 2 IMH represents a good alternative to vitrectomy for patients with IMH.

INTRODUCCIÓN: Los agujeros maculares idiopáticos (AMI) son comunes y afectan la visión central. Demostramos la efectividad de 0.2 ml de perfluoropropano (C3F8) intravítreo en AMI en estadio 2. CASO: Una mujer de 61 años presentó con visión borrosa súbita OD. Mejor agudeza visual corregida (MAVC) 20/125 OD y 20/20 en el OS. La biomicroscopía del OD evidenció un AMI en estadio 2. Se inyectó C3F8 intravítreo y se prescribieron medidas posturales. Una semana después, la tomografía de coherencia óptica reveló desprendimiento de vítreo posterior. La resolución de tracción vitreomacular con recuperación anatómica y funcional completa se logró a la semana 4 y se mantuvo estable durante un seguimiento de 6 meses (MAVC 20/20 OD). CONCLUSIÓN: El C3F8 intravítreo como terapia inicial para AMI en estadio 2 representa una buena alternativa a la vitrectomía vía pars plana en pacientes con AMI.

Long-term visual and anatomic outcomes after photodynamic therapy for symptomatic circumscribed choroidal hemangioma.

Circumscribed choroidal hemangiomas (CCHs) are relatively rare. We report the response of a symptomatic CCH to photodynamic therapy (PDT). A 70-year-old male presented with blurred vision of the left eye (OS). Best-corrected visual acuity (BCVA) was 20/60 right eye and 20/160 OS. Biomicroscopy revealed bilateral cataracts. Diagnosis of CCH was made fundoscopically for OS and confirmed with optical coherence tomography (OCT). One session of PDT with individualized parameters was administered. After 2 months, anatomical improvement was evidenced with OCT and BCVA was 20/60. After cataract surgery, his BCVA was of 20/25 and remained stable. PDT showed excellent anatomic and visual results after a 2-year follow-up.

Los hemangiomas coroideos circunscritos son relativamente raros. Reportamos la respuesta de uno sintomático con terapia fotodinámica. Un hombre de 70 años presentó visión borrosa en el ojo izquierdo. La mejor agudeza visual corregida fue de 20/60 en el ojo derecho y de 20/160 en el izquierdo. La biomicroscopía demostró catarata en ambos ojos. En el ojo izquierdo se diagnosticó un hemangioma coroideo circunscrito confirmado con tomografía de coherencia óptica. Se administró una sesión de terapia fotodinámica con parámetros individualizados. Dos meses después se observó mejoría anatómica en la tomografía de coherencia óptica, y la mejor agudeza visual corregida fue de 20/60. Después de la cirugía de catarata, la mejor agudeza visual corregida fue de 20/25 y tuvo estabilidad. La terapia fotodinámica mostró excelentes resultados anatómicos y funcionales a los 2 años.

Anatomical Changes of Full-Thickness Macular Hole Documented by Microscope-Integrated Spectral-Domain Optical Coherence Tomography.

BACKGROUND AND OBJECTIVE: To evaluate anatomical changes of idiopathic macular hole (MH) after internal limiting membrane removal and after passive suction at the hole's borders using microscope-integrated intraoperative optical coherence tomography (iOCT). PATIENTS AND METHODS: Five eyes of five subjects with full-thickness idiopathic MH underwent phacoemulsification, intraocular lens implantation, pars plana vitrectomy, and internal limiting membrane (ILM) removal. iOCT was performed after ILM removal and after passive suction at the hole's borders. RESULTS: iOCT showed decreased MH diameter after ILM removal in all cases. Passive suction achieved complete apposition of borders. All cases presented successful postsurgical closure. CONCLUSIONS: iOCT provides anatomical information during MH surgery that may impact surgical decision-making by allowing a real-time evaluation of structures. iOCT with preservative-free triamcinolone acetonide enhanced ILM visualization. Its use is superior to iOCT alone for the identification of vitreomacular interface structures. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e105-e111.].

Short-term outcomes after the loading phase of intravitreal bevacizumab and subthreshold macular laser in non-center involved diabetic macular edema.

AIM: To compare the effectiveness of intravitreal bevacizumab and subthreshold macular photocoagulation (SMP), for the treatment of non-center involved diabetic macular edema (non-CI DME). METHODS: Prospective, randomized, controlled clinical study included patients with type 2 diabetes, non-CI DME and best-corrected visual acuity (BCVA) of 0.30 logMAR or better. Each eye was randomized into three groups: group 1, monthly intravitreal bevacizumab; group 2, single SMP; group 3, single SMP and monthly bevacizumab. Main outcome measures were BCVA, and macular thickness measured with optical coherence tomography as macular central subfield thickness (CST), macular area of greater thickness (MAGT) and total macular volume (TMV). Results were analyzed after 3mo. RESULTS: A total of 32 eyes were included. Group 3 improved in BCVA (0.19±0.16 to 0.12±0.14 logMAR; P=0.041) and in TMV (7.90±0.57 to 7.65±0.73 mm3; P=0.025). Group 1 improved in MAGT (325±26.26 to 298.20±44.85 µm; P=0.022) and TMV (7.79±0.57 to 7.50±0.56 mm3, P=0.047). Group 2 didn't show significant improvement of any variable. CONCLUSION: The loading phase of bevacizumab as monotherapy or combined with SMP is superior to SMP as monotherapy in providing short-term visual and anatomical improvement in non-CI DME.

Minimally Invasive Surgery for the Removal of Posterior Intraocular Foreign Bodies.

This is a prospective clinical assay that included six patients who were diagnosed with penetrating corneal injury, traumatic cataract, and posterior segment intraocular foreign body (IOFB). Following anterior segment repair and extraction of traumatic cataract by clear cornea phacoemulsification, a standard 25-gauge transconjunctival pars plana vitrectomy was performed to find and release the IOFB. With active suction using a 25-gauge silicone tipped cannula, the foreign body was retrieved and safely placed in the anterior chamber. After stabilization of the anterior chamber with viscoelastic injection, IOFB extraction through the main phaco incision was easily performed, followed by placement of an intraocular lens. Of the six patients, 66.6% showed a significant improvement of visual acuity. No complications associated directly with the surgical procedure occurred. Our surgical technique is a safe alternative for handling and removing a posterior IOFB. There was no need for a scleral incision.

[Intraoperative use of coherence tomography in vitreoretinal surgery]. / Utilidad transquirúrgica de la tomografía de coherencia óptica en cirugía vítreo-retiniana.

BACKGROUND: Optical coherence tomography is a useful tool in several diseases. Its intraoperative use with the intention of improving anatomical results has recently been described. PURPOSE: To determine the usefulness and safety of optical coherence tomography during pars plana vitrectomy for several vitreo-retinal diseases. MATERIAL AND METHODS: A prospective case series is reported, in which the decision that influenced the use of the optical coherence tomography imaging during pars plana vitrectomy is evaluated. A RESCAN 700 microscope that includes a spectral domain tomography was used to obtain the images. At the end of each procedure the surgeons completed a questionnaire to determine if the tomographic image had an influence when making decisions during the surgery, or change the decision during the procedure. RESULTS: Thirteen patients with pars plana vitrectomy were included, with cataract surgery also performed in 6 patients. The surgeon considered that the intraoperative image influenced the decision during the procedure in 8 cases. CONCLUSION: Intraoperative optical coherence tomography is helpful for a safe patient diagnosis. It does not affect the surgery time, and in some cases it is useful for optimising the procedure in vitreous-retinal surgery.