Manifestations of intraocular inflammation over time in patients on brolucizumab for neovascular AMD.

PURPOSE: To describe the adverse events associated with brolucizumab, in particular the sequence of intraocular inflammation (IOI), retinal vasculitis (RV), and/or retinal vascular occlusion (RO). METHODS: This was an unmasked post hoc analysis of the randomized HAWK/HARRIER clinical trials. Patients with neovascular AMD in the brolucizumab arms of the trials were included. IOI-related adverse events reported by study investigators were analyzed to determine early signs and the time course of IOI-related adverse events, using a subgroup of patients with definite/probable IOI cases identified in an independent unmasked post hoc review by an external safety review committee. A limited literature review on IOI following anti-VEGF therapy was also conducted. RESULTS: Among 50 patients with definite/probable IOI cases identified by the safety review committee, 12 had RV or RO adverse events reported by the investigators. For 6 of 12, IOI (other than RV) was reported before RV or RO. The duration from the first IOI adverse event to the first RV or RO adverse event ranged from 16 to 171 days for 5 patients and was 553 days for 1 patient. Four of the 6 patients received ≥ 1 brolucizumab injection on or after the date of the first IOI adverse event and before the first RV or RO adverse event. CONCLUSIONS: IOI may precede RV or RO in some patients treated with brolucizumab.

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.

[The Role of Intraoperative Microscope-Integrated OCT in Retinal Surgery. Part 1: Pro]. / Stellenwert der intraoperativen optischen Kohärenztomografie in der Netzhautchirurgie. Teil 1: pro.

Novel microscope-integrated OCT now allows targeted intraoperative high-resolution real-time imaging. In comparison to conventional surgical microscopes, intraoperative real-time OCT visualisation of retinal layers and vitreous body provides valuable information for surgical decision-making. In addition, simultaneous OCT imaging of retinal structures displayed within the funduscopic view through the eye-piece of the microscope allows direct guidance of instrument-tissue interaction and surgical manoeuvres. As a result, targeted iOCT imaging enables enhanced precision and the development of real-time guided surgical techniques at micron level.

[Intraoperative Optical Coherence Tomography in Vitreoretinal Surgery: Clinical Experiences and Future Developments]. / Die intraoperative optische Kohärenztomografie in der Netzhaut-Glaskörper-Chirurgie. Aktuelle Erfahrungen und Ausblick auf künftige Entwicklungsschritte.

PURPOSE: High resolution optical coherence tomography (OCT) enables better visualization of ophthalmic microstructures than conventional imaging. When using an ophthalmic microscope, integrated optical coherence tomography (iOCT) high resolution real time visualization is possible. METHODS: We report on the first 110 patients operated on using a microscope integrated OCT (iOCT) during surgical procedures for the treatment of various posterior segment pathologies. RESULTS: Microstructural changes that appeared during surgery were depicted precisely by iOCT, and the morphology visualized before and after each surgical step was used to help deciding how to adapt the surgical flow. The iOCT data and real-time imaging of retinal anatomy gives the surgeon the possibility of deploying patient- and operation-specific interventional procedures. DISCUSSION: To date, iOCT is only available in standing microscopes with no measurement or tracking features. Moreover, metal instruments currently obscure the scanned images. In the future, non-metal, transparent instruments (OCT-friendly surgical tools), tracking features, an autofocus and higher resolution could enable full and immediate intraoperative SD-OCT diagnostics in real time.

Platelet activation by ADP is increased in selected patients with anterior ischemic optic neuropathy or retinal vein occlusion.

To investigate whether adenosine diphosphate (ADP)-induced platelet hyperaggregability is associated with nonarteritic anterior ischemic optic neuropathy (NAION) or retinal vein occlusion (RVO). We retrospectively reviewed thrombophilia screening data of patients with NAION or RVO without a history of arterial hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette abuse. Patients with a positive family history for thromboembolism were not excluded. Platelet aggregation (area under the curve, AUC) after induction of 0.5, 1.0, and 2.0 µmol of ADP was estimated in 25 NAION and RVO patients and compared with 25 healthy controls. We observed significantly greater platelet aggregation post 0.5 (P = 0.002) and 1.0 (P = 0.008) µmol of ADP among NAION and RVO patients compared with healthy controls. Platelet hyperaggregability was significantly more prevalent in patients than in controls (56% vs. 8%; P = 0.0006). Our results suggest that in NAION and RVO patients without a history of arterial hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette abuse, platelets are significantly hyperreactive after induction of very low concentrations of ADP when compared with healthy individuals. This hyperreactivity is particularly evident in patients with a family history of thromboembolism.

Intravitreal Sustained-Release Steroid Implants for the Treatment of Macular Edema following Surgical Removal of Epiretinal Membranes.

PURPOSE: To evaluate the efficacy of intravitreal dexamethasone implant for the treatment of postoperative persistent cystoid macular edema (CME) following macular pucker surgery. METHODS: In this multicenter study, we retrospectively reviewed the data of 37 patients (39 eyes) who had been treated with intravitreal dexamethasone implant (Ozurdex®) for persistent CME following macular pucker surgery. Main outcome measures were change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS: All eyes underwent spectral domain optical coherence tomography examination within 130 days after implantation. We observed a significant decrease in mean CRT from 519.9 to 392.9 µm (p < 0.0001). By this time, mean BCVA had improved from 0.60 to 0.43 logMAR (p = 0.003). Seventeen eyes (43.6%) required at least 1 repeat injection of dexamethasone. Of these, 8 (47%) eyes received a total number of 3 or more dexamethasone injections. CONCLUSION: Intravitreal dexamethasone implant injection is an effective treatment option for persistent CME following macular pucker surgery.

Selective Thrombophilia Screening in Young Patients with Retinal Artery Occlusion.

PURPOSE: To investigate the prevalence of various thrombophilic disorders among young patients with retinal artery occlusion (RAO). PROCEDURES: We retrospectively reviewed thrombophilia screening data of young patients ≤60 years of age with RAO and healthy controls matched for gender and age. RESULTS: Thrombophilia screening data of 25 young patients and 62 healthy controls were analyzed. Mean patient age by the time of the RAO was 43.3 ± 10.8 years. Overall, thrombophilic defects were found to be present in 17 patients (68%) compared with 11 of 62 controls (17.7%; p < 0.0001). Multivariate logistic regression analysis confirmed a statistically significant association between the development of RAO and increased levels of lipoprotein(a) (odds ratio: 9.48; p = 0.001) and factor VIII (odds ratio: 6.41; p = 0.024). There was a strong association between the presence of thrombophilic disorders and a personal or family history of thromboembolism (p = 0.01). CONCLUSIONS: Our results indicate that screening for thrombophilic disorders among selected young patients with RAO yields positive results in a high percentage of cases.

Intravitreal ranibizumab versus isovolemic hemodilution in the treatment of macular edema secondary to central retinal vein occlusion: twelve-month results of a prospective, randomized, multicenter trial.

PURPOSE: This is a prospective, randomized, multicenter, investigator-initiated trial to evaluate the 12-month effectiveness of isovolemic hemodilution (IH) with prompt versus deferred intravitreal injections (IVI) of ranibizumab 0.5 mg for the treatment of macular edema secondary to early central retinal vein occlusion (CRVO). METHODS: Eyes with macular edema due to CRVO having occurred not more than 8 weeks previously received either monthly ranibizumab IVI in combination with IH (group I, n = 28) or IH alone (group II, n = 30). From month 2 to 12, the patients in both groups could be treated with monthly intravitreal ranibizumab. The main outcome variables were gain of visual acuity and the course of central retinal thickness as measured with optical coherence tomography. RESULTS: At 12 months, eyes in group I on average gained +28.1 (±19.3) letters compared to +25.2 (±20.9) letters in group II (p = 0.326). This result was achieved with significantly fewer injections in group II. Additionally, 30% of the eyes in group II did not need ranibizumab IVI during the 12 months of the trial. CONCLUSION: Ranibizumab IVI in addition to IH proved to be highly effective in increasing visual acuity and reducing macular edema secondary to CRVO. Initial IH in early CRVO may be a first treatment option in patients anxious about IVI.

Retrospective, observational study in patients receiving a dexamethasone intravitreal implant 0.7 mg for macular oedema secondary to retinal vein occlusion.

PURPOSE: To retrospectively evaluate the re-injection interval, efficacy and safety of dexamethasone (DEX) intravitreal implant 0.7 mg in the treatment of macular oedema (ME) due to retinal vein occlusion (RVO) in Germany in 2009-2012. METHODS: Retrospective, multicentre, anonymised observational study of data collected from the first DEX implant 0.7 mg injection through 3-6 months following the last injection. Data were included if the patient was >18 years old, had a diagnosis of ME secondary to branch or central RVO, and received at least 2 DEX implant 0.7 mg injections during routine practice. RESULTS: Data from 87 patients were analysed. Mean time to re-injection between first and second treatments was 5.03 months in the total RVO population, and 5.46 and 4.52 months for the branch and central RVO subpopulations, respectively. An intraocular pressure increase of >25 mm Hg was recorded in 20% of patients, and 34% of patients began treatment with anti-glaucoma medication, but surgery was not needed for this condition. CONCLUSIONS: DEX implant 0.7 mg was found to be well tolerated and effective with repeat treatments in clinical practice.

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.

[Macular hole: Differential diagnosis, treatment options and new guideline recommendations]. / Makulaforamen: Differenzialdiagnose, Behandlungsoptionen und neue Leitlinienempfehlungen.

Full-thickness macular holes (FTMH) usually result in a pronounced reduction of visual acuity and represent one of the most frequent indications for retinal surgery. If diagnosed and treatment is initiated at an early stage, surgery has a high success rate with respect to both hole closure and improvement of visual acuity. Optical coherence tomography (OCT)-based staging and sizing enables an estimation of the surgical outcome. The differential diagnostic distinction from clinically similar disorders, such as lamellar macular holes, macular pseudoholes, and foveoschisis is clinically relevant as the pathogenesis, prognosis and treatment are significantly different. While vitrectomy with peeling of the inner limiting membrane (ILM) and gas tamponade is established as the standard treatment for FTMH, some aspects of treatment are handled differently between surgeons, such as the timing of surgery, the choice of endotamponade and the type and duration of postoperative positioning. For FTMH associated with vitreomacular traction, alternative treatment options in addition to vitrectomy include intravitreal ocriplasmin injection and pneumatic vitreolysis. The current clinical guidelines of the German ophthalmological societies summarize the evidence-based recommendations for diagnosis and treatment of FTMH.

[Lamellar macular holes-In the center of vitreomacular interface diseases : Pathophysiology, spontaneous courses and treatment concepts]. / Makulaschichtforamen ­ im Zentrum der vitreomakulären Grenzflächenerkrankungen : Pathophysiologie, Spontanverläufe und Therapiekonzepte.

BACKGROUND: A lamellar macular hole (LMH) is characterized by a distinct morphologic configuration and can be distinguished from related entities such as macular pseudohole (MPH) and epiretinal membrane with foveoschisis (ERM-FS) by clear morphologic features. PURPOSE: Based on current knowledge, the pathophysiologic function of LMH in the spectrum of vitreomacular interface diseases will be described and therapeutic concepts will be presented. METHODS: Current studies are supplemented by case reports to provide a schematic overview of the natural history and therapeutic concepts at the vitreomacular interface. RESULTS: The LMH is as a retrospective marker for pathologic posterior vitreous detachment in adult patients and may be interpreted as the pathophysiologic center of tractional maculopathies. Various vitreomacular pathologies can result in LMH: a detached vitreomacular traction, a spontaneously closed penetrating macular hole, or an epiretinal membrane with foveoschisis. Pathophysiologically, a degenerative, progressive loss of the architecture of the foveal muller cell cone may be the underlaying mechanism, resulting in the typical undermining of the hole edges and occasionally in a full thickness macular hole. The optimal timing and the appropriate surgical method are the focus of current clinical studies. CONCLUSION: The pathophysiology of LMH indicates a smooth transition of tractive maculopathies. These should be prospectively evaluated in order to develop evidence-based treatment strategies for LMH.

[Vitreomacular traction: diagnostics, natural course, treatment decision and guideline recommendations]. / Vitreomakuläre Traktion: Diagnostik, natürlicher Verlauf, Therapieentscheidung und Leitlinienempfehlungen.

Vitreomacular traction is a tractive foveolar adhesion of the posterior vitreous limiting membrane, resulting in pathological structural alterations of the vitreomacular interface. This must be differentiated from physiological vitreomacular adhesion, which exhibits a completely preserved foveolar depression. Symptoms depend on the severity of the macular changes and typically include reduced visual acuity, reading problems and metamorphopsia. High-resolution spectral domain optical coherence tomography (SDOCT) imaging enables classification of the sometimes only subtle morphological changes. If pronounced vitreomacular traction is accompanied by epiretinal gliosis and alterations to the outer retina, it is referred to as a vitreomacular traction syndrome. Vitreomacular traction has a high probability of spontaneous resolution within 12 months. Therefore, treatment should only be carried out in cases of undue suffering of the patient and with symptoms during bilateral vision and a lack of spontaneous resolution. In addition to pars plana vitrectomy, alternative treatment options, such as intravitreal injection of ocriplasmin and pneumatic vitreolysis are discussed for vitreomacular traction with an associated macular hole; however, ocriplasmin is no longer available in Germany. The best anatomical results in comparative investigations were achieved by vitrectomy. Pneumatic vitreolysis is controversially discussed due to the increased risk of retinal tears. In one of the current S1 guidelines of the German ophthalmological societies evidence-based recommendations for the diagnostics and treatment of vitreomacular traction are summarized.

[Epiretinal membrane: diagnostics, indications and surgical treatment]. / Epiretinale Gliose: Diagnostik, Indikationsstellung und chirurgische Therapie.

An epiretinal membrane (ERM) is a frequently occurring disease affecting the macula, which can be associated with visual impairment and metamorphopsia, depending on the severity and location. A distinction is made between an idiopathic form caused by age-related changes of the vitreous body and a secondary form associated with diseases of the posterior segment. The development of fibrocellular epiretinal membranes formed by dedifferentiation of intraretinal and extraretinal cells at the level of the vitreomacular interface plays a major role in the pathogenesis. The diagnostics and indications for surgical treatment of ERM are based on the visual acuity, evidence of metamorphopsia, ophthalmoscopic findings and optical coherence tomography (OCT) of the macula. In addition to the possibility of observation of the course where benign spontaneous courses are not uncommon, pars plana vitrectomy (PPV) with peeling of the ERM and internal limiting membrane (ILM) to prevent recurrences is the treatment of choice in symptomatic patients. The prognosis after surgical treatment is very good. In approximately two thirds of the cases, an improvement in visual acuity and/or a reduction of metamorphopsia can be achieved, with a number of predictive, primarily OCT-based factors enabling a prediction of the functional prognosis. Comprehensive patient education regarding the generally long duration of postoperative rehabilitation and the possibility of persistent symptoms or visual deterioration despite successful membrane removal is essential.

Early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial.

RATIONALE: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data are lacking to address this question. AIMS: The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO. METHODS: This study is the randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. STUDY OUTCOMES: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best-corrected visual acuity of the Logarithm of the Minimum Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomography/angiography, ultrasound and magnetic resonance imaging (MRI) biomarkers will be conducted. SAMPLE SIZE: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha = 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. DISCUSSION: By enrolling patients within 4.5 h of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may translate to CRAO with its similar pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

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.

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.

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.