Die Ophthalmologie最新文献

Background: Retinal ischemia plays a central pathophysiological role in numerous eye diseases, such as glaucoma. In addition to apoptosis, autophagy, necroptosis and ferroptosis are among the cell death mechanisms of ischemia; however, their role is not clearly understood and controversially discussed.

Objective: The aim of this study is to gain an improved understanding of the role of alternative cell death mechanisms such as autophagy and necroptosis after retinal ischemia. Based on this, future autophagy-based or necroptosis-based therapeutic approaches could be developed.

Material and methods: Retinal ischemia reperfusion was induced in one eye of 6 to 8‑week-old rats by temporarily increasing the intraocular pressure to 140 mm Hg (60 min), followed by reperfusion. The untreated contralateral eye served as a control. Retinas after ischemia and control retinas were examined 7 days after ischemia immunohistochemically with markers for retinal ganglion cells (RGC), astrocytes (GFAP) as well as an autophagy (LAMP1) and a necroptosis marker (RIPK3) (n = 6/group).

Results: Ischemia reperfusion resulted in both significant RGC loss (p ≤ 0.001) and a significant increase of astrocyte area (p = 0.026) after 7 days. Interestingly, the number of autophagic LAMP1 positive cells was unchanged 7 days after ischemia (p = 0.272), whereas the number of necroptotic RIPK3 positive cells was significantly increased (p ≤ 0.001).

Conclusion: Necroptotic processes appear to be activated 7 days after ischemia reperfusion, contributing to retinal cell death and activation of astrocytes. Late autophagic processes are not activated 7 days after ischemia. Necroptosis-associated parameters could therefore be targeted as an early therapeutic approach after ischemia in the future.

Background: AURIGA is the largest prospective real-world study to evaluate intravitreal aflibercept 2 mg (IVT-AFL) treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) and diabetic macular edema. Here we present the 24-month data from the German cohort of treatment-naïve patients with ME due to RVO.

Methods: Treatment-naïve patients with ME secondary to RVO were treated with IVT-AFL 2 mg in the routine clinical practice. The primary endpoint was mean change in visual acuity (VA, early treatment diabetic retinopathy, ETDRS, letters) at month 12 compared to baseline. Analyses were descriptive.

Results: Analysis included 130 patients with RVO (n = 61, 46.9% with central RVO, n = 69, 53.1% with branch RVO). The mean (± SD) time the RVO patients remained in the study was 18.4 ± 7.4 months. The mean VA gain (95% confidence interval) in the overall cohort was +10.9 (7.5-14.2) letters at month 12 and +9.7 (6.1-13.3) at month 24 (baseline VA 56.5 ± 18.9 letters). At 24 months, 67% of RVO patients gained ≥5 letters and 40% gained ≥15 letters. The mean number of injections was 4.4 ± 1.3 up to month 6, 6.2 ± 2.7 up to month 12 and 8.2 ± 4.5 up to month 24. The mean central retinal thickness (CRT) reduction was -206µm (-252 to -160µm) at 12 months and -219µm (-263 to -175µm) at 24 months (baseline CRT 507 ± 177 µm). The safety profile was consistent with that of previous studies.

Discussion: In the German AURIGA cohort of treatment-naïve patients with ME secondary to RVO, IVT-AFL 2 mg treatment in clinical practice resulted in rapid and clinically relevant VA gains and a reduction in CRT. These results were largely maintained over 24 months despite the low injection frequency from month 6.

Approximately 0.5-1% of patients with multiple sclerosis (MS) have co-existing uveitis. Both intraocular inflammation and MS mainly affect women in younger adulthood. The MS in patients is most frequently associated with an often bilateral intermediate uveitis with typical concomitant retinal vasculitis. Both diseases share similar characteristics with chronic inflammatory diseases with a relapsing course and an immune-mediated pathogenesis; however, it is still unclear whether the co-occurrence of uveitis and MS in the same patient represents a coincidence of two separate disease entities or whether uveitis is a rare clinical manifestation of MS. In the differential diagnostics of intermediate uveitis, clinical symptoms and signs of MS should be considered. As both diseases are considered to be immune-mediated, immunotherapy is the main treatment option. In recent years the range of medications has expanded and includes several disease modifying drugs (biologics). When selecting the active substance it must be taken into account that tumor necrosis factor (TNF) alpha blockers are contraindicated in patients with MS.

Clinical features: The click phenomenon occurs when an acquired mechanical restriction of the elevation in adduction of the eye or of the extension of the finger/thumb, is forcefully overcome. The common cause is a nodule either of the superior oblique tendon posterior to the trochlea in the case of a Jaensch-Brown syndrome or of the digital flexor tendon anterior to the A1 annular pulley in the case of a trigger finger. Both locations share similar anatomical conditions for the development of the nodule and the pathomechanism of the click.

Results: From these identical findings in the eye and the hand in small children it can be assumed that the results from the studies of the hand in newborns and infants with a trigger thumb/finger are also applicable to the situation of the eye. 1. This motility disorder is not congenital. This is most likely due to an incomplete development at the time of birth of the sliding factors needed for a free passage of the tendon through the trochlea and the A1 annular pulley. 2. A distinction must be made between stages 0-3: stage 0 = no more restriction of the motility and no click phenomenon; stage 1 = forced active extension/elevation possible; stage 2 = only passive extension/elevation, each with a click phenomenon; stage 3 = no extension/elevation possible and no click phenomenon. 3. In most cases in early childhood there is a spontaneous complete recovery (75% after 6-7 years). In the eye this spontaneous course can only limitedly be shortened with motility exercises in combination with segmental occlusion.

Conclusion: The click phenomenon is a symptom of stages 1 and 2 of an acquired mechanical restriction of the elevation in adduction of the eye or the extension of the finger/thumb. It should not be called a syndrome.

Advances in imaging and artificial intelligence (AI) have revolutionized the detection, quantification and monitoring for the clinical assessment of intermediate age-related macular degeneration (iAMD). The iAMD incorporates a broad spectrum of manifestations, which range from individual small drusen, hyperpigmentation, hypopigmentation up to early stages of geographical atrophy. Current high-resolution imaging technologies enable an accurate detection and description of anatomical features, such as drusen volumes, hyperreflexive foci and photoreceptor degeneration, which are risk factors that are decisive for prediction of the course of the disease; however, the manual annotation of these features in complex optical coherence tomography (OCT) scans is impractical for the routine clinical practice and research. In this context AI provides a solution by fully automatic segmentation and therefore delivers exact, reproducible and quantitative analyses of AMD-related biomarkers. Furthermore, the application of AI in iAMD facilitates the risk assessment and the development of structural endpoints for new forms of treatment. For example, the quantitative analysis of drusen volume and hyperreflective foci with AI algorithms has shown a correlation with the progression of the disease. These technological advances therefore improve not only the diagnostic precision but also support future targeted treatment strategies and contribute to the prioritized target of personalized medicine in the diagnostics and treatment of AMD.