Brolucizumab for recalcitrant macular neovascularization in age-related macular degeneration with pigment epithelial detachment.

PURPOSE: To analyze anatomic and functional response to intravitreal brolucizumab in age-related macular degeneration recalcitrant to previous intravitreal anti-VEGF therapies. METHODS: In this monocentric, one arm, retrospective study, eyes affected by neovascular age-related macular degeneration (nAMD) resistant to other intravitreally injected anti-vascular endothelial growth factor inhibitors were switched to intravitreal brolucizumab. All patients underwent ophthalmological examinations at baseline and in regular follow-up intervals. Best registered visual acuity (BRVA), Goldmann tonometry, intraocular pressure (IOP), central retinal thickness (CRT) and pigment epithelial detachment (PED) characteristics were analyzed at initiation of anti-VEGF treatment, at treatment switch, and at the end of brolucizumab loading phase. RESULTS: The study included 20 eyes of 18 consecutively treated patients (age: 77 ± 6 years). All eyes had macular neovascularization with PED. Previous treatments included intravitreal aflibercept, bevacizumab, and ranibizumab and had not resulted in a significant improvement in BRVA (0.5 ± 0.5 logMAR vs 0.5 ± 0.6 logMAR) or mean CRT (320 ± 60 µm vs 313 ± 83 µm) up to treatment switch to brolucizumab. At the end of the brolucizumab loading phase, there was significant improvement for both BRVA (0.3 ± 0.2 logMAR, P < 0.05) and CRT (264 ± 55 µm, P < 0.05). Under previous anti-VEGF therapy, there was a significant increase/deterioration in both PED area (2.68 mm2 to 5.18 mm2, P < 0.05) and PED volume (0.39 mm3 to 1.07 mm3, P < 0.05); however, both parameters improved after switching to brolucizumab (3.81 mm2 and 0.37 mm3, P < 0.05). CONCLUSION: Our results suggest a favourable anatomical and visual response after treatment switch to brolucizumab in patients with nAMD refractory to previous anti-VEGF agents.

Acute central retinal artery occlusion with emboli.

CRAO is an ophthalmic and medical emergency. This case is a reminder that diagnosis and management of CRAO begins with ophthalmologists but immediately thereafter care involves emergency cardiovascular and neurological similar to cerebral stroke.

Isolated Internal Ophthalmoplegia from Posterior Cerebral Artery Neurovascular Conflict.

We report a rare case of recurrent isolated internal ophthalmoplegia attributed to oculomotor nerve (CN III) compression by the posterior cerebral artery (PCA). A 30-year-old female patient presented with recurrent right-sided headaches, right periorbital pain, and slight anisocoria. Slit-lamp examination revealed normal anterior and posterior segments except for vermiform movements of the right pupil with a temporal hyporeactive flat area. Tonic pupils were ruled out with pilocarpine 0.1% testing. Suspecting an internal ophthalmoplegia, magnetic resonance imaging was ordered which demonstrated the right CN III indented by the PCA, fulfilling the criteria of a neurovascular conflict. The evaluation of unilateral mydriasis from internal ophthalmoplegia should prompt neuroimaging with exclusion of aneurysmal or compressive lesions. CN III palsy can rarely be caused by vascular anatomical variants because of the proximity of the posterior intracranial circulation and CN III. Newer, more precise imaging techniques will better help characterize neurovascular conflicts presenting as cranial nerve palsies.

Frosted branch angiitis as an immune recovery response in newly diagnosed acquired immunodeficiency syndrome and systemic cytomegalovirus infection.

Frosted branch angiitis (FBA) is an uncommon form of severe retinal perivasculitis associated with systemic inflammatory/infectious diseases. In this report, we describe a case of FBA and macular edema as a result of immune recovery response in a patient newly diagnosed with HIV infection and cytomegalovirus viremia.

A Narrative Review - Therapy Options and Therapy Failure in Retinoblastoma.

Retinoblastoma (RB) management has evolved over the last three decades. Goals of modern RB treatment are first to protect life and prevent metastatic disease, then preservation of the globe and useful vision. With modern treatment protocols and early disease detection success rates can reach up to 100% of disease-free-globe and eye preservation. Treatment of advanced cases remains complex, requiring aggressive chemotherapy or/and external beam radiation. Treatment protocols are extremely diverse and dependent on local resources thus success rates are variable. Here we review narratively current treatment protocols and failure rates based on a PubMed search using keywords of retinoblastoma, retinoblastoma seed, retinoblastoma treatment, enucleation.

Real-Time (iOCT) Guided Epiretinal Membrane Surgery Using a Novel Forceps with Laser-Ablated Microstructure Tip Surface.

PURPOSE: We investigated intraoperative OCT (iOCT)-guided epiretinal membrane (ERM) and internal limiting membrane (ILM) removal using a novel forceps with a laser-ablated tip surface; it was designed to help prevent indentation force, shear stress, or tractional trauma when grasping very fine membranes. PATIENTS AND METHODS: This retrospective study included patients who underwent 23- and 25-gauge pars plana vitrectomy (PPV) for vitreoretinal interface disorders. ERM and ILM peeling was performed under guidance with microscope-integrated iOCT using novel ILM forceps with laser-ablated tip surfaces. These forceps were engineered to enhance friction when grasping tissue. Evaluation of ERM/ILM manipulation included postoperative slow-motion video analysis of the number of grasping attempts, initial ILM mobilization, and observed damage to retinal tissue. RESULTS: ERM/ILM removal was successfully performed in all patients, with an average of four grasp actions to initial membrane mobilization (91%). Additional use of a diamond-dusted membrane scraper was used in two cases (9%). Mean best-recorded visual acuity (BRVA) logMAR improved from 0.5 ± 0.34 to 0.33 ± 0.36 (p = 0.05) and mean central retinal thickness (CRT) improved from 462 ± 146 µm to 359 ± 78 µm (p = 0.002). Postoperative iOCT video analysis demonstrated hyper-reflectivity of the inner retinal layers associated with retinal hemorrhage in five eyes (22%), but no grasping-related retinal breaks. CONCLUSIONS: The texturized surface on the tips of the ILM forceps were found to be helpful for mobilizing ILM edges from the retinal surface. iOCT-guided ERM surgery also allowed for improved intraoperative tissue visualization. We believe that these two technologies helped reduce both unnecessary surgical maneuvers and retinal damage.

Intravitreal fluocinolone acetonide implant for chronic postoperative cystoid macular edema - two years results.

PURPOSE: We report visual and anatomical outcomes of chronic postoperative macular edema treated with a fluocinolone acetonide intravitreal implant. METHOD: Retrospective study of chronic, post-surgical CME treated with a fluocinolone acetonide intravitreal implant. Best registered visual acuity (BRVA), central retinal thickness (CRT), and Goldmann tonometry intraocular pressure (IOP) were assessed over 24 months. The need for IOP lowering treatment, top-up therapy during follow-up, and complications were also assessed. RESULTS: We analyzed 16 consecutive eyes of 16 patients with chronic, post-surgical CME treated with fluocinolone acetonide intravitreal implant. Surgical indications included cataract surgery, vitrectomy plus membrane peeling and combined phaco-vitrectomy. Baseline mean BRVA of 0.8 ± 0.65 logMAR improved to 0.60 ± 0.4 logMAR (p = 0.02) at 12 months and to 0.7 ± 0.5 logMAR (p = 0.32) at 24 months. At month 12, BRVA improved in 11 eyes, stabilized in 4 eyes, and decreased in 1 eye. At month 24, VA remained improved in 5 eyes, remained stabilized in 5 eyes, and decreased in 1 eye. Mean CRT decreased from 524 ± 132 µm at baseline to 389 µm at month 3, 347 µm at month 6, 355 ± 106 µm (p = 0.0003) at month 12, and 313 ± 83 µm (p = 0.0001) at month 24. At 12 months, CRT improved in 13 eyes and remained unchanged in 2 eyes. At 24 months, CRT improved further in 8 eyes, and stabilized in 3 eyes. Increased IOP (≥21 mmHg) was observed only in 4 eyes, all successfully managed with topical medication. No further side effects were observed in any patient. CONCLUSION: Visual and anatomic improvements were achieved by a single fluocinolone acetonide implant with few side effects up to 24 months in CME eyes with a long and heavy prior treatment history.

Primary Vitreoretinal Lymphoma Therapy Monitoring: Significant Vitreous Haze Reduction After Intravitreal Rituximab.

BACKGROUND/AIMS: Intravitreal rituximab is an off-label treatment option for primary vitreoretinal lymphoma (PVRL). The objective of this study was to monitor the therapeutic response and safety profile of intravitreal rituximab in a cohort of PVRL patients. METHODS: In this retrospective, uncontrolled, open label, multicentre study, 20 eyes from 15 consecutive patients diagnosed with PRVL received at least one intravitreal injection of 1mg in 0.1ml rituximab. Biodata of the PVRL patients was recorded as well as visual acuity and vitreous haze score immediately before rituximab intravitreal injection and at follow-up examinations. Intravitreal rituximab safety data was also recorded. Additional rituximab injections were made during control visits on a pro re nata (PRN) regime using increased vitreous haze to indicate recurrence. RESULTS: There was significant vitreous haze reduction (p=0.0002) followed by significant improvement of visual acuity (mean best visual acuity before therapy 0.57 logMAR, after therapy 0.20 logMAR (p=0.0228) during the follow-up time up to 4 years. Only mild ocular side effects were reported. Median follow-up time was 565 days (range, 7-1253 days). CONCLUSION: Intravitreal rituximab therapy shows promising PVRL regression without any severe side effects. Although our clinical data support rituximab as intravitreal therapy in PVRL disease, further study is warranted.

Pneumatic retinopexy: A critical reappraisal.

Pneumatic retinopexy (PR) has been widely advocated for treatment of selected rhegmatogenous retinal detachments: those with small, anterior, superior, retinal breaks and little or no proliferative vitreoretinopathy. It has been suggested that PR is underused and is advantageous because it is an outpatient clinic or office procedure, short in duration, nonincisional, and cost saving - with reduced perioperative morbidity, faster postoperative recovery, better and faster visual recovery, a low rate of complications and a high rate of overall success compared with scleral buckling or pars plana vitrectomy. We reevaluated these advantages to substantiate the effectiveness and efficiency of PR and critically define its role in the treatment of rhegmatogenous retinal detachment. We found that PR has a much higher rate of subsequent reoperation and proliferative vitreoretinopathy than scleral buckling or pars plana vitrectomy for simple, good prognosis rhegmatogenous retinal detachments. PR often involves multiple procedures that largely negates its potential cost savings and subjects the patient to prolonged stress and disability. Scleral buckling rather than PR is ideally suited for simple, good prognosis rhegmatogenous retinal detachments for surgeons who feel comfortable with the technique; alternatively, pars plana vitrectomy is indicated.

Treatment of radiation maculopathy and radiation-induced macular edema: A systematic review.

Radiation maculopathy and radiation-induced macular edema are common, sight-threatening complications after radiotherapy, especially that used for uveal melanoma. While many treatment and preventive strategies have been proposed, management of these conditions is still challenging. Initially, treatments were based on the use of retinal laser, but the outcomes were poor. Subsequently, management has shifted toward injection of intravitreal antivascular endothelial growth factor or corticosteroids. We reviewed current clinical evidence, which mostly relies on small sample-sized and retrospective studies, for the management of radiation maculopathy and, in particular, radiation-induced macular edema. At present, the first-line approach is usually intravitreal antivascular endothelial growth factor. Intravitreal dexamethasone implantation may be an option for those with suboptimal response or contraindications to antivascular endothelial growth factor agents. Possible preventive treatments that require future study are intravitreal bevacizumab and ranibizumab, peripheral laser photocoagulation, and subtenon triamcinolone acetonide.

Combined Topical Anti-inflammatory and Oral Acetazolamide in the Treatment of Central Serous Chorioretinopathy.

SIGNIFICANCE: Central serous chorioretinopathy (CSCR) is still a therapeutic challenge with no criterion standard treatment. However, anatomic changes at the level of the retinal pigment epithelium could prove of predictive value in the course of the disease for selective treatment in cases of increased risk of chronicity. PURPOSE: This pilot study analyzes the efficacy for treating acute CSCR with combined systemic acetazolamide 250 mg twice a day and nepafenac 0.1% eye drops three times a day in comparison with an untreated control group. It also evaluates the presence a pigment epithelial detachment (PED) as a risk factor for chronic CSCR. METHODS: Nineteen consecutive patients (group 1) with new or new onset of recurrent CSCR were treated with oral acetazolamide and nepafenac eye drops for at least 2 months. A control group of 14 patients (group 2) with new or new onset of recurrent CSCR were untreated while under regular observation for 4 months. Primary end points were central macular thickness and best-corrected visual acuity after 4 months. Secondary end points were complete regression of subretinal fluid at 3 months and association of PED at baseline with recurrent or chronic CSCR imaged by optical coherence tomography. RESULTS: Group 1 showed significantly faster resolution of subretinal fluid with a mean central macular thickness at 4 months of 271 ± 85 µm compared with 322 ± 79 µm for group 2 (P < .05), but with no functional benefit with a best-corrected visual acuity at 4 months of 0.8 ± 0.2 for group 1 compared with 0.9 ± 0.1 for the control group (P < .05). Patients with a small flat PED were at a higher risk of developing chronic CSCR compared with patients with a dome-shaped or no PED (P < .05). CONCLUSIONS: Central serous chorioretinopathy remains a therapeutic challenge. This pilot study shows faster resolution of subretinal fluid with treatment but without functional benefit compared with observation. The presence of small, flat PED was associated with development of chronic CSCR.

Central retinal artery occlusion-A new, provisional treatment approach.

The retinal ganglion cells infarcted in central retinal artery occlusion (CRAO) are the somata of the optic nerve axons, part of the central nervous system. Consequently, CRAO with inner retinal infarction is a small vessel stroke, usually with the devastating consequence of severe visual loss in the affected eye. At present, there is no generally accepted, evidence-based therapy of nonarteritic CRAO in contrast to ischemic cerebral stroke that has well-accepted treatment protocols. Widely divergent and controversial therapeutic options for CRAO reflect the desperation of treating physicians and disparate conflicting studies. We examine reasons why treatment of nonarteritic CRAO remains problematic and then suggest a provisional new approach to treatment based on updated understanding of CRAO pathophysiology and analysis of current therapeutic options and their rationales.

Occult globe rupture: diagnostic and treatment challenge.

Occult globe rupture is a traumatic dehiscence of the sclera at or posterior to the rectus muscle insertions without a visible eye wall defect on slit lamp examination. Occult scleral ruptures are important because they can be difficult to diagnose, but normally require preoperative protection against external pressure to reduce risk of herniation of ocular contents through the rupture and then urgent surgical repair to restore eye wall structural integrity and achieve optimum prognosis. A deeper-than-normal anterior chamber with posteriorly retracted plateau iris seen immediately after acute ocular trauma is virtually pathognomonic of posterior globe dehiscence. Three additional less specific signs are helpful: extensive chemosis that is often hemorrhagic, relative hypotony, and vitreous hemorrhage. Although the diagnosis is normally clinical, made by history of direct severe ocular trauma and careful anterior-segment slit lamp examination, computed tomography and ultrasonography can be helpful when thorough slit lamp examination is not possible. Strong suspicion of occult rupture should engender surgical exploration. Vitreous hemorrhage, vitreous or retinal incarceration, and retinal tears or detachment may necessitate subsequent pars plana vitrectomy or other vitreoretinal surgery. When pars plana vitrectomy is indicated, special precautions are suggested if watertight closure of the globe rupture has not been possible.

Central retinal artery occlusion - rethinking retinal survival time.

BACKGROUND: The critical time from onset of complete occlusion of the central retinal artery (CRA) to functionally significant inner retinal infarction represents a window of opportunity for treatment and also has medical-legal implications, particularly when central retinal artery occlusion (CRAO) complicates therapeutic interventions. Here, we review the evidence for time to infarction from complete CRAO and discuss the implications of our findings. METHODS: A Medline search was performed using each of the terms "central retinal artery occlusion", "retinal infarction", "retinal ischemia", and "cherry red spot" from 1970 to the present including articles in French and German. All retrieved references as well as their reference lists were screened for relevance. An Internet search using these terms was also performed to look for additional references. RESULTS: We find that the experimental evidence showing that inner retinal infarction occurs after 90-240 min of total CRAO, which is the interval generally accepted in the medical literature and practice guidelines, is flawed in important ways. Moreover, the retinal ganglion cells, supplied by the CRA, are part of the central nervous system which undergoes infarction after non-perfusion of 12-15 min or less. CONCLUSIONS: Retinal infarction is most likely to occur after only 12-15 min of complete CRAO. This helps to explain why therapeutic maneuvers for CRAO are often ineffective. Nevertheless, many CRAOs are incomplete and may benefit from therapy after longer intervals. To try to avoid retinal infarcton from inadvertent ocular compression by a headrest during prone anesthesia, the eyes should be checked at intervals of less than 15'.