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.

Intravitreal Brolucizumab for Pachychoroid Neovasculopathy Associated With Chronic Central Serous Chorioretinopathy.

Purpose: To evaluate the anatomical and functional outcomes of intravitreal brolucizumab in eyes with chronic central serous chorioretinopathy complicated by pachychoroid neovasculopathy. Methods: Retrospective analysis of 34 eyes treated with intravitreal brolucizumab. Twenty-five eyes (73.5%) had been treated with other anti-vascular endothelial growth factor agents before switching to brolucizumab, whereas nine eyes were naïve. Outcome measures included the change of central foveal thickness and subfoveal choroidal thickness, evaluation of sub/intraretinal fluid on optical coherence tomography, and change in best-corrected visual acuity. Results: Before starting brolucizumab, 23 eyes showed subretinal fluid, 8 both subretinal and intraretinal fluid, and 3 intraretinal fluid only. At the last visit, 22 eyes (64.7%) showed complete reabsorption of both intraretinal and subretinal fluid, whereas subretinal fluid was still present in 8 eyes (23.5%), and both intraretinal and subretinal fluid in 4 eyes (11.8%). The mean number of brolucizumab injections required to achieve complete fluid reabsorption was 2.8 ± 1.8. central foveal thickness decreased from 317.8 ± 109.3 µm to 239.8 ± 74.8 µm (P = 0.0005) and subfoveal choroidal thickness decreased from 399.3 ± 86.2 µm to 355.5 ± 92.7 µm at the end of the follow-up period (P = 0.0008). The mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.4 ± 0.2 to 0.3 ± 0.2 at 1 month after the first injection and remained stable at the same values at the end of the follow-up period (P = 0.04). Conclusions: Intravitreal brolucizumab is effective for the treatment of naïve and recalcitrant pachychoroid neovasculopathy. Translational Relevance: Intravitreal brolucizumab may represent an option in patients with pachychoroid neovasculopathy complicating chronic central serous chorioretinopathy.

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.

[Retinal vein occlusion : Intravitreal pharmacotherapies and treatment strategies for the management of macular edema]. / Venöse retinale Gefäßverschlüsse : Intravitreale Therapien und Strategien zur Behandlung des Makulaödems.

Intravitreal injection treatment for the management of macular edema as an expression of increased capillary permeability and leakage constitute the mainstay of treatment in retinal vein occlusion. In contrast to diabetic retinopathy or neovascular age-related macular degeneration, permanent and complete functional and morphological restoration can be achieved, as retinal vein occlusions are usually associated with risk factors, but do not represent the manifestation form of an underlying systemic or degenerative chronic disorder; however, successful long-term management of retinal vein occlusion -associated macular edema usually requires intensive and also long-term continued treatment with vascular endothelial growth factor (VEGF) inhibitors or with a less favorable side effect profile, dexamethasone. A functional treatment success can be maintained over the long term by both pro re nata (PRN) or treat and extend (T&E) regimens. In contrast, according to the currently available data, the combination of anti-VEGF administration and grid laser treatment has no additional benefit compared to monotherapy. In patients with recalcitrant macular edema, switching to another intravitreal agent may be considered during the course of treatment, although a true therapeutic benefit with respect to the development of visual acuity has not yet been proven. The current review summarizes the relevant aspects in the management of RVO-associated macular edema and provides the foundations for the application of successful treatment strategies.

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.

[Clinical aspects and care of radiogenic treatment side effects on the eye]. / Klinik und Versorgung von radiogenen Behandlungsnebenwirkungen am Auge.

Malignant tumors of the eye can be successfully treated with radiotherapy, which, however, can lead to radiogenic side effects in the surrounding healthy tissues. A  distinction can be made between two forms of irradiation, external radiotherapy (teletherapy) and brachytherapy with a radiation source close to the tumor. The radiation dose is important for the occurrence of side effects. Acute damage usually results from inflammatory processes initiated at the cellular level. In contrast, late side effects are rather due to the reaction of the tissue with repair and remodeling processes . Acute side effects often resolve completely, especially under corresponding treatment, whereas late side effects tend to be irreversible. The aim of this article is to present risk factors as well as the clinical signs of periocular and ocular radiogenic side effects for the relevant tissue structures of the eye in a narrative review to facilitate ophthalmologic follow-up and, if necessary, treatment measures for these patients during everyday practice.

Switching to intravitreal fluocinolone acetonide implant for refractory diabetic macular edema: 12- and 24-month results.

PURPOSE: To report visual and anatomical outcomes of chronic/refractory diabetic macular edema (DME) treated with intravitreal fluocinolone acetonide implant. SETTING: Retrospective, one arm, multicentric study. METHOD: Between 2013 and 2018, 27 consecutive eyes of 25 patients with chronic/refractory DME were treated with a fluocinolone acetonide intravitreal implant. Best registered visual acuity (BRVA), central retinal thickness (CRT), and Goldmann tonometry intraocular pressure (IOP) were assessed at 12 and 24 months. The need for IOP lowering treatment as well as top-up therapy during the follow-up were also assessed. RESULTS: The duration of DME prior to treatment in our study was 54 ± 24 months. The baseline mean BRVA of 0.7 ± 0.34 logMAR improved to 0.5 ± 0.3 (p = 0.01) at 12 months and 0.46 ± 0.3 (p = 0.04) at 24 months. At 12 months, BRVA improved in 14 eyes (52%), stabilized in 5 eyes (20%), and decreased in 3 eyes (11%). At 24 months, BRVA improved further in 6 eyes (24%), stabilized in 3 eyes (12%), and decreased in 6 eyes (24 %). Mean CRT decreased from 497 ± 176 to 349 ± 186 µm at 12 months (p = 0.0005) and to 267 ± 104 µm at 24 months (p = 0.001). Only five eyes required additional treatment for DME and only three eyes required treatment for raised IOP. DISCUSSION: Our results show that the visual and the anatomical improvements achieved by a single injection of a fluocinolone acetonide implant were maintained up to 24 months with minimal additional therapy even in eyes with a long and heavy history; however, IOP monitoring remains essential.

Surgical Management of Choroidal Diseases. / Chirurgisches Management bei Erkrankungen der Aderhaut.

Accumulation of serous fluid in the suprachoroidal space, known as uveal effusion, and choroidal or suprachoroidal haemorrhage (SCH) following rupture of ciliary blood vessels are considered rare, but serious, events with extremely poor functional prognosis. As a result, uveal effusion, and expulsive suprachoroidal haemorrhage in particular, continue to be considered as more or less fatal complications. However, clinical experience demonstrates that both clinical entities can be managed by conservative as well as surgical strategies, depending on their severity and localisation, with sometimes surprisingly favourable visual outcome. In addition to prognostic factors, timely recognition and prompt, if possible preventive, acute care, as well as carefully considered timing of adequate surgical measures taking advantage of the specific characteristics of the choroidal tissue, are crucial to treatment success. Along with technical advances in the field of vitreoretinal surgery, numerous variants of therapeutic approaches to the treatment of choroidal effusion and suprachoroidal haemorrhage have been proposed to date. This review presents some of the most important surgical techniques and strategies in the field.

Ophthalmic Outpatient and Inpatient Care Under Pandemic Conditions: Hygiene, Triage and New Challenges. / Ambulante und stationäre Augenheilkunde unter Pandemiebedingungen: Hygiene, Triage und neue Herausforderungen.

BACKGROUND: The progression of the COVID-19 pandemic has caused significant changes in the environment for outpatient and inpatient care in ophthalmology, with limitations on access to medical care but also new observations and challenges. We now describe major developments in recent months and provide an outlook on the expected consequences. METHODS: PubMed literature search, clinical survey. RESULTS: To date, the course of the COVID-19 pandemic has been characterised by several new but overall rare ocular manifestations, the ophthalmological shared management of COVID-19 patients on intensive care units, and a significant decrease in case numbers, associated with an increase in case severity and relative proportion of emergencies, as a result of delayed presentation of patients and reduced treatment adherence. With the introduction of hygiene measures and infection control procedures, ophthalmic patient care was maintained - including emergencies and urgent treatments. Due to the extensive postponement of elective surgeries, scarce therapeutic and health care professional resources, and the prioritisation of critically ill patients from other specialties, there is a reasonable likelihood that urgent treatments will be delayed as infection rates rise. CONCLUSION: Outpatient and inpatient care in ophthalmology during the COVID-19 pandemic is primarily accompanied by additional organisational or medical challenges and a decline in case volume. Although to date emergency and urgent ophthalmic treatments have been maintained, long-term persistence of pandemic conditions will require additional strategies to provide continuation of ophthalmic care at the required level.

[Ocular involvement in Stevens-Johnson syndrome and toxic epidermal necrolysis]. / Okuläre Beteiligung bei Stevens-Johnson-Syndrom und toxisch epidermaler Nekrolyse.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare severe and often life-threatening reactions of the skin and mucous membranes. They are considered as a single disease entity with different expressions of severity and are summarized under the term epidermal necrolysis (EN). There is a high risk of ocular involvement, which can lead to long-lasting eye problems and even blindness without immediate ophthalmological treatment. The acute occurrence, the unpredictable course and extreme variation in the manifestation of complications require an interdisciplinary approach. A rapid diagnosis of eye involvement and initiation of an intensive lubricating and anti-inflammatory surface treatment is of utmost importance for the long-term outcome. This article should help ophthalmologists to have a better understanding of this condition and therefore lead to substantial improvement in visual outcome and the quality of life of patients.

The significance of pigment epithelial detachment in central serous chorioretinopathy.

PURPOSE: To investigate the significance of the presence and form of pigment epithelial detachment in the course of central serous chorioretinopathy as well as corticosteroid use as a risk in our patient cohort. MATERIAL AND METHODS: Retrospective, single center study of central serous chorioretinopathy patients between January 2013 and January 2019 recording corticosteroid use prior to onset and presence and type of pigment epithelial detachment (flat-irregular, dome-shaped, none) in relationship to disease course. RESULTS: We analyzed 53 eyes of 53 consecutive central serous chorioretinopathy patients treated in our department. Mean patient age was 53 ± 13 years. A flat-irregular pigment epithelial detachment was associated with either chronic or recurrent central serous chorioretinopathy, whereas the absence of a pigment epithelial detachment correlated positively with acute central serous chorioretinopathy (chi-square test, p < 0.05). Of the 53 patients, 10 reported corticosteroid use, 40 denied steroid use, and 3 patients failed to make a clear statement. Corticosteroid use was not correlated with the onset of central serous chorioretinopathy (Student's t-test, p = 0.0001, chi-square test, p < 0.005). CONCLUSION: A small, flat-irregular pigment epithelial detachment could be a marker for chronic or recurrent central serous chorioretinopathy, whereas the absence of pigment epithelial detachment could favor acute central serous chorioretinopathy. Advanced imaging studies may provide more information on the exact characteristics and nature of pigment epithelial detachments. Corticosteroid use as possible disease trigger was not confirmed in this study.

Factors predicting normal visual acuity following anatomically successful macular hole surgery.

PURPOSE: To assess the incidence of normal vision following anatomically successful macular hole surgery and associated clinical variables. METHODS: Multicentre, retrospective chart review. Preoperative, intraoperative and postoperative clinical data were extracted from electronic medical records from seven European vitreoretinal units. Inclusion criteria were as follows: eyes undergoing primary vitrectomy for idiopathic full-thickness macular hole from January 2015 to January 2018; postoperative macular hole closure confirmed by spectral domain optical coherence tomography (OCT); preoperative pseudophakia or phakic eyes receiving combined cataract surgery; one-year follow-up. The primary outcome was 'normal vision' defined as a final best-corrected visual acuity (BCVA) ≥ 20/25. Univariate, multivariate and decision-tree analyses were conducted to evaluate the clinical variables associated with 'normal vision'. Odds ratios (OR) and confidence intervals (CIs) were calculated. RESULTS: Of 327 eligible cases, 91 (27.8%) achieved 'normal vision' at 1 year. Multivariate analysis identified variables significantly associated with 'normal vision': shorter symptom duration (odds ratio [OR]=1.05; 95% confidence interval [CI]:1.02-1.09; p = 0.002), smaller preoperative OCT minimum linear diameter (OR per 100-micron increase = 1.65; 95%CI:1.31-2.08; p < 0.001) and better mean preoperative BCVA (OR = 15.13; 95%CI: 3.59-63.65; p < 0.001). The decision-tree analysis found that the most significant variable associated with 'normal vision' was symptom duration. 'Normal vision' was achieved in 70.6% of eyes operated within one week from symptom onset and in 45% of eyes with symptom duration between 1 and 3 weeks. CONCLUSIONS: These findings suggested urgent surgery is justified for small macular holes of short duration.

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.