Rubella virus-associated uveitis at a tertiary care hospital in Germany between 2013 and 2019.

Uveitis is a process of intraocular inflammation that may involve different sections of the uveal tract. Apart from systemic or localized immune-mediated diseases, infections are key players in the etiology of uveitis and entail different treatment strategies. Rubella virus (RuV) is a recognized causative agent for the development of Fuchs uveitis, representing a major cause of virus-associated intraocular inflammation. A cohort of 159 patients diagnosed with different forms of uveitis between 2013 and 2019 was subjected to diagnostic antibody testing of the aqueous or vitreous humor. The diagnostic panel included RuV, cytomegalovirus, herpes simplex virus, varicella-zoster virus, and toxoplasmosis. Within this cohort, 38 RuV-associated uveitis (RAU) patients were identified based on a pathologic Goldman-Witmer coefficient indicative of an underlying RuV infection. With a mean age of 45.9 years, the RAU patients were younger than the non-RAU patients (56.3, p < 0.001). The evaluation of clinical parameters revealed a predominance of anterior uveitis and late sequalae such as cataract and glaucoma among the RAU patients. In 15 of the patients a history of prior RuV infections could be confirmed. The study underlines the importance of long-term surveillance of RuV associated diseases that originate from infections before the introduction of RuV vaccination programs.

Prognostic Factors in Patients with Persistent Full-Thickness Idiopathic Macular Holes Treated with Re-Vitrectomy with Autologous Platelet Concentrate.

PURPOSE: To identify the predictors for anatomical and functional outcome after re-vitrectomy with application of autologous platelet concentrate (APC) in eyes with persistent idiopathic macular hole (MH). METHODS: Retrospective study of 103 eyes with persistent MHs after vitrectomy with peeling of internal limiting membrane (ILM) and expansive gas. All patients underwent re-vitrectomy with APC and endotamponade. The anatomical MH closure rate and postoperative best-corrected visual acuity (BCVA) were evaluated. Further, predictive factors influencing the success of the surgery were analyzed. RESULTS: Median BCVA (logMAR) before the surgery was 1.00 (interquartile range [IQR] 0.80-1.30) and the median of minimum diameter between hole edges was 508 µm (IQR 387-631). The final closure rate after re-vitrectomy with APC was 60.2% (62 of 103 eyes). The following predictors were identified to significantly influence the closure rate: tractional hole index (THI), axial length, time between first and second surgery, and the experience of the surgeon (p < 0.05). CONCLUSIONS: Re-vitrectomy with APC led to the closure of 60.2% of the persistent MHs. The closure rate negatively correlates with increasing axial length, time between the first and second surgery, and the decreased THI. Further, experienced surgeons (with a history of >100 pars plana vitrectomies with ILM peeling) had significantly higher closure rates.

Thrombospondin-1 is produced by retinal glial cells and inhibits the growth of vascular endothelial cells.

BACKGROUND/AIMS: By the release of antiangiogenic factors, Müller glial cells provide an angiostatic environment in the normal and ischemic retina. We determined whether Müller cells produce thrombospondin-1 (TSP-1), a known inhibitor of angiogenesis. METHODS: Secretion of TSP-1 by cultured Müller cells was determined with ELISA. Slices of rat retinas and surgically excised retinal membranes of human subjects were immunostained against TSP-1 and the glial marker vimentin. The effects of TSP-1 on the growth of bovine retinal endothelial cells (BRECs) and activation of ERK1/2 were determined with DNA synthesis and migration assays, and Western blotting, respectively. RESULTS: Cultured Müller cells secrete TSP-1 under normoxic and hypoxic (0.2% O2) conditions. Secretion of TSP-1 was increased in hypoxia compared to normoxia. In rat retinal slices, glial, retinal ganglion, and possibly horizontal cells were stained for TSP-1. Retinal glial cells in preretinal membranes from human subjects with nonhypoxic epiretinal gliosis (macular pucker) and proliferative diabetic retinopathy, respectively, were immunopositive for TSP-1. Exogenous TSP-1 reduced the VEGF-induced proliferation and migration of BRECs and decreased the phosphorylation level of ERK1/2 in BRECs. CONCLUSION: The data suggest that Müller cells are one major source of TSP-1 in the normal and ischemic retina. Glia-derived TSP1 may inhibit angiogenic responses in the ischemic retina.

General health of patients with diabetic macular edema-The LIPSIA study.

PURPOSE: Cardiovascular risk factors such as hypertension or dyslipidemia can influence the incidence and progression of diabetic retinopathy (DR) and diabetic macular edema (DME). The aim of this study is to describe the comorbidities in patients with DME. METHODS: Prospective, monocentric observational study. Patients presenting for the treatment of DME received laboratory and clinical examinations including 24-hour blood pressure measurement. RESULTS: Seventy-five consecutive patients were included in the study. The mean age was 61.0 ± 14.5 years, and 83% had type 2 diabetes. The mean body mass index (BMI) was 32.8 ± 6.0 kg/m2. Overweight (BMI ≥ 25 kg/m2) was present in 92% of all patients. HbA1c values were > 7.0% in 57%. Although 87% of the patients already received antihypertensive therapy, the blood pressure (BP) of 82% was still above the recommended target values of systolic < 140 mmHg and diastolic < 80 mmHg. An insufficient nocturnal fall of the systolic BP (< 10%, non-dipping or reverse dipping) was observed in 62%. In 83% of the patients the glomerular filtration rate was ≤ 90 ml/min/1.73m2. Despite 65% of the cohort already receiving lipid-lowering therapy, LDL cholesterol was above the target value of 1.4 mmol/l in 93%. All patients had at least one cardiovascular risk factor in addition to diabetes (overweight, hypertension, insufficient nocturnal BP fall, dyslipidemia, or renal dysfunction) and 86% had ≥ 3 risk factors. CONCLUSION: DME patients are characterized by highly prevalent cardiovascular risk factors that are poorly controlled. These comorbidities reduce the prognosis and negatively influence existing DR and DME. The data reveal an important opportunity for improving patient care by interaction of the ophthalmologist with the general practitioner and internal specialists for the detection and treatment of these conditions.

Different modes of foveal regeneration after closure of full-thickness macular holes by (re)vitrectomy and autologous platelet concentrate.

AIM: To describe using spectral-domain optical coherence tomography the regeneration of the foveal morphology after pars plana (re)vitrectomy surgery and gas tamponade combined with injection of autologous platelet concentrate to treat full-thickness macular holes, and to describe different anatomical outcome. METHODS: A retrospective case series of 8 eyes of 8 patients was described. RESULTS: In all cases investigated, the platelet-assisted closure of macular holes was associated with a rapid resolution of cystic cavities in the foveal walls. In two patients, there was a regular regeneration of the foveal morphology after hole closure; the regenerated central fovea had a regular structure with a foveola and photoreceptors. In three other patients, there was an irregular regeneration of the fovea; a foveola was not formed, photoreceptor cells were absent from the foveal center, and the center was composed of Müller and retinal pigment epithelial (RPE) cells. The foveal regeneration after hole closure may proceed with or without a temporary detachment of the foveal center from the RPE, and with or without a direct contact between the central outer nuclear layer (ONL) and the RPE. Contacts between the ONL and RPE were observed only in patients with an irregular foveal regeneration after hole closure. CONCLUSION: The data show that there are different modes of foveal regeneration after closure of macular holes with (re)vitrectomy and platelet concentrate. It is suggested that the regular regeneration of the foveal morphology proceeds by Müller cell-mediated tissue movements without cell proliferation, whereas the irregular foveal regeneration proceeds in part by proliferation of Müller and RPE cells.

Outcomes in diabetic macular edema switched directly or after a dexamethasone implant to a fluocinolone acetonide intravitreal implant following anti-VEGF treatment.

AIMS: Fluocinolone acetonide (FAc) is an intravitreal corticosteroid implant approved for the second-line treatment of diabetic macular edema (DME). This study compared outcomes of patients with DME switched directly to an FAc implant, versus indirectly via dexamethasone, after anti-VEGF therapy failure. METHODS: This is a retrospective, single-center chart review. Patients were assigned to Group A (switched to FAc after anti-VEGF) or Group B (switched to dexamethasone and then to FAc after > 4 months). Charts were reviewed for best-corrected visual acuity (BCVA), central macular thickness (CMT), intraocular pressure (IOP) and cataract development. RESULTS: Forty-nine eyes were included. BCVA increased and CMT decreased with anti-VEGF (both groups), and dexamethasone (Group B only), but regressed after stopping treatment. With FAc, BCVA increased rapidly and significantly: increases were maintained up to 36 months (P < 0.001), except at 18 and 9 months in Groups A and B, respectively. Significant CMT reductions (P < 0.001) were evident after 3 months and maintained up to 36 months in both groups. IOP increase > 21 mmHg occurred in 14 patients (nine in Group A, five in Group B): all were sufficiently treated with IOP-lowering drops. Nineteen phakic eyes (73.1%) developed cataract: seven underwent phaco-emulsification (two in Group A, five in Group B). CONCLUSIONS: Similar functional and anatomical improvements occurred in FAc-treated eyes, regardless of whether they first received dexamethasone or switched directly to FAc after anti-VEGF. Safety signals were consistent with corticosteroid class effects. Early switch to FAc could benefit patients who respond insufficiently to anti-VEGF.

Spontaneous closure of small full-thickness macular holes: Presumed role of Müller cells.

PURPOSE: To document with spectral domain optical coherence tomography the formation and spontaneous closure of small full-thickness macular holes and to propose the active role of Müller cells in macular hole closure. METHODS: A retrospective case series of five patients with spontaneous closure of macular holes is reviewed. In one patient, foveal images were recorded over a period of 18 months. RESULTS: In a 66-year-old man, vitreofoveal traction caused a detachment of the inner Müller cell layer of the foveola from the outer nuclear layer (ONL) which was associated with a large pseudocyst and a horizontal gap in the central ONL. The traction caused an elongation and subsequent disruption of the stalk of the Müller cell cone in the foveola. A small full-thickness macular hole developed when a portion of the inner Müller cell layer of the foveola was pulled out. After phacoemulsification and shortly before the subsequent spontaneous closure of the hole, there were rapid increases in the number and size of the cystic cavities in the foveal walls resulting in a narrowing of the hole. The hole closed by bridging the gap in the inner part of the central ONL; a new inner Müller cell layer of the foveola was formed, and the gap of the external limiting membrane (ELM) was closed. The cystic cavities in the foveal walls rapidly disappeared within 2 weeks after the closure of the hole. One to 2.5 months after hole closure, the thickness of the central ONL increased which decreased the distance between the central ELM and retinal pigment epithelium. In three of the four other patients, the hole also closed by bridging the gap in the inner part of the ONL. CONCLUSION: It is suggested that the spontaneous closure of small macular holes and the subsequent reconstruction of the normal foveal structure are mediated by active mechanisms of Müller cells which resemble those involved in ontogenetic foveal development.

Aflibercept for Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice in Germany: Twelve-Month Outcomes of PERSEUS.

PURPOSE: To explore real-world effectiveness of intravitreal aflibercept injection (IAI) for neovascular age-related macular degeneration (nAMD) in Germany. DESIGN: A 24-month, prospective, noninterventional, noncontrolled, multicenter observational cohort study. PARTICIPANTS: Patients (n = 848) with nAMD treated with IAI. METHODS: Patients (n = 988) were screened at 67 study sites. Therapeutic decisions were made by the treating physician. Primary end point analysis was performed after 12 months for the entire study cohort and for predetermined subgroups of treatment-naïve and previously treated patients. Additionally, outcomes with regular injection intervals (bimonthly after 3 monthly injections) were compared with those of patients with irregularities in their treatment regimen. MAIN OUTCOME MEASURES: The primary end point was the mean change in visual acuity (VA) from baseline after 12 months. Other key end points included the proportions of patients gaining 15 letters or more and patients with reading vision (≥70 letters). Furthermore, the number of injections, anatomic measurements, and safety data were recorded. RESULTS: Mean ± standard deviation VA improvement was 5.3±17.4 letters in treatment-naïve patients and -0.1±15.6 letters in previously treated patients (P ≤ 0.0001), and that of the total study group was 2.9±16.8 letters. Baseline VA was 53.4±17.9 letters for treatment-naïve patients, 52.9±18.4 letters for previously treated patients, and 53.2±18.1 letters for the total patient population. Treatment pattern was associated with VA outcome: best outcomes-an average VA gain of 8.0±17.7 letters-were seen in treatment-naïve patients in the regularly treated population, whereas irregularly treated, treatment-naïve patients achieved a mean VA gain of only 4.0±17.1 letters. Among previously treated patients, regular treatment also was associated with better outcomes (+3.1±10.7 vs. -1.1±16.8 letters). For the total study group, the mean VA gain was the following: regularly treated population, 6.1±15.6 letters; irregularly treated population, 1.5±17.1 letters (P = 0.008). No cases of endophthalmitis were observed during the first 12 months of the study. Adverse events were in line with the known safety profile of IAI. CONCLUSIONS: After 12 months of treatment with IAI, treatment-naïve patients showed substantial functional benefit, whereas previously treated patients maintained their VA. With regular IAI treatment, it seems that similar results as those in pivotal IAI studies can be achieved in routine clinical practice.

Complications after photodynamic therapy.

OBJECTIVE: To evaluate the incidence of complications of photodynamic therapy (PDT) with verteporfin in subfoveal choroidal neovascularizations secondary to age-related macular degeneration and pathologic myopia. METHODS: In this retrospective interventional case series, the occurrence of complications after PDT in a clinical setting was analyzed. Consecutive medical records of patients with age-related macular degeneration and pathologic myopia treated with PDT were reviewed for complications. Complications included treatment-related systemic adverse events, injection site effects, and ocular adverse events. RESULTS: We included 273 patients (198 with age-related macular degeneration and 75 with pathologic myopia) in the study. A total of 485 photodynamic treatment sessions were performed. Infusion-related back or chest pain was reported by 6 patients (2.2%; 95% confidence interval [CI], 0.8%-4.7%). Injection site effects, extravasation, and photosensitivity reactions were not observed. Dyspnea and flushing during infusion were observed in 2 patients (0.7%; 95% CI, 0.09%-2.6%). Body pain, shortness of breath, and elevated blood pressure were noted in 13 patients (4.8%; 95% CI, 2.6%-8.0%). General pruritus was described by 6 patients (2.2%; 95% CI, 0.8%-4.7%), starting 4 hours after the infusion of verteporfin, and resolved within 72 hours after PDT. A total of 8 patients (2.9%; 95% CI, 1.3%-5.7%) reported an acute severe visual acuity decrease of at least 4 Early Treatment Diabetic Retinopathy Study lines occurring within 7 days of treatment. CONCLUSIONS: Complications associated with PDT are uncommon, but there were limitations of retrospective studies for identifying safety problems. Complications like acute severe visual events may occur in about 3% of patients. We believe that this risk is outweighed by the benefits of PDT on visual function in most patients.

[Epidemiology, pathogenesis and therapy of diabetic retinopathy and maculopathy]. / Epidemiologie, Pathogenese, Diagnostik und Therapie der diabetischen Retinopathie und Makulopathie.

Diabetic retinopathy is the most prevalent microvascular complication of diabetes mellitus and affects the majority of patients who have suffered diabetes for at least 20 years. Due to the lack of specific symptoms screening of patients is required for early retinal lesions to be detected. Chronic hyperglycemia plays a predominant role in the pathogenesis of the disease. A common denominator of hyperglycemic vascular injury is the increased production of mitochondrial reactive oxygen species, leading to the activation of protein kinase C, of the aldose reductase pathway, and to the increased formation of advanced glycation end products, with the well-described deleterious effects on the microvasculature. Moreover, hypertension and factors such as puberty and pregnancy can worsen retinopathy. Effective screening and therapy can prevent blindness. A distinction is made between proliferative and non-proliferative diabetic retinopathy and diabetic macula oedema. The professional associations of ophthalmologists and internists have drawn up guidelines for the necessary examinations, for therapy and the appropriate intervals between check-ups. Laser photocoagulation can halt further loss of vision, in particular in cases of proliferative diabetic retinopathy and diabetic macula oedema. Vitrectomy is an operative procedure that can bring about a functional improvement even for patients in advanced stages.

[Comparison of risk factors and guideline oriented prevention and therapy of diabetic retinopathy between type 2 diabetes patients undergoing laser therapy and type 2 diabetes outpatients]. / Vergleich der Risikoparameter der diabetischen Retinopathie und der leitliniengerechten Prävention für Patienten einer diabetischen Schwerpunktambulanz und eines Lasertherapiezentrums.

PURPOSE: The purpose of this study was the comparison of risk factors for development or progression of diabetic retinopathy in patients with type 2 diabetes between patients of a laser therapy center and a diabetes outpatient clinic. Furthermore, the implementation of the guidelines of the German Diabetic Association for the prevention and therapy of diabetic retinopathy was analysed. PATIENTS AND METHODS: In a prospective study, patients with type 2 diabetes and diabetic retinopathy of the laser therapy center at the ophthalmology department, Leipzig University, were interviewed and examined. Patients of the reference group without diabetic retinopathy were recruited from the diabetes outpatient clinic Leipzig University. RESULTS: Between August 2004 and May 2008, a total of 180 patients with type 2 diabetes were included (48 patients with non-proliferative diabetic retinopathy (NPDR), 59 patients with proliferative diabetic retinopathy (PDR) and 73 patients belonging to the reference group). Patients with diabetic retinopathy had significantly higher mean blood pressures of 112 and 110 mmHg as compared to patients without diabetic retinopathy (96 mmHg). ACE/ AT1-inhibitors were used significantly less by patients with as compared to patients without diabetic retinopathy. Only 37% of patients with diabetic retinopathy were treated according to DDG and ADA guidelines. CONCLUSION: There are striking deficits for the implementation of guideline oriented prevention and therapy of diabetic retinopathy in daily practice. The possible reasons are insufficient compliance of patients who consulted medical advice only when complications of diabetes occurred, the necessary improvement of the medical therapy and the suboptimal cooperation between ophthalmology and diabetes specialists.

Quantitative assessment of the long-term effect of photodynamic therapy in patients with pathologic myopia.

BACKGROUND: In patients with classic subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia (PM), photodynamic therapy (PDT) has been shown to stabilize the visual acuity. We have analyzed the long-term visual prognosis after PDT in patients with CNV secondary to PM. METHODS: In a retrospective study we reviewed the clinical charts of 102 patients. PDT was performed following the procedures described in the VIP and TAP study protocols. Follow-up examinations and PDT treatment were scheduled in 3-month intervals. Indications for retreatment were an active leaking CNV in combination with visual disturbances or visual loss. To assess treatment effects we analyzed the number of letters read on the ETDRS charts. The primary efficacy outcome was the proportion of eyes that had fewer than eight letters loss or gain at 24 months. Secondary efficacy outcomes included the proportion of eyes that had fewer than 15 letters loss or gain and the proportion of eyes that had fewer than 30 letters loss or gain at month 24. RESULTS: One hundred and two patients were included into the study. Mean follow-up was 32.5+/-5.7 months. Patients received an average of 2.2 treatments from study entry through the last follow-up, resulting in a total of 221 PDT sessions throughout the study. At 24 months 46% lost at least eight letters. A loss of at least 15 (30) letters was observed in 25% (8%). Improvement of at least eight letters was noted in 8%. Larger improvements of at least 15 letters occurred only in 4% of study eyes. CONCLUSION: Our study suggests that PDT can increase the chance of stabilizing or improving vision compared with the placebo arm of VIP trial.

Angiographic findings in patients with exudative age-related macular degeneration.

PURPOSE: Exudative age-related macular degeneration (ARMD) is the leading cause for severe visual loss in the elderly. A series of clinical trials has established the efficacy of laser photocoagulation and photodynamic therapy (PDT) in special subgroups of patients with exudative ARMD. We analyzed the fluorescein and indocyanine green angiograms (ICG) of patients with exudative ARMD to characterize the nature of the CNV in order to estimate the percentage of patients amenable for one of the therapies. METHODS: Patients with acute symptoms related to exudative ARMD were recruited for the study. All patients underwent fluorescein and ICG angiography. We analyzed the type of the CNV (classic, occult, or mixed) and location relative to the fovea from the fluorescein angiograms. Additionally, we recorded the presence of a visible capillary network in the early ICG angiograms, as well as hot spots and plaque hyperfluorescence in the late ICG angiographic frames. RESULTS: We included 191 patients aged 53-92 years in the study. The angiograms revealed in 17 (9%) patients classic CNV (12 subfoveal), in 114 (60%) occult CNV, and in 60 (31%) mixed CNV. Of these 19 had a classic component >50%. In the early ICG angiograms a capillary network was visible in 50 eyes with occult CNV. Hot spots were present in 29 eyes and a hyperfluorescent plaque in 54 eyes. CONCLUSION: In total, only 18% of eyes included in our study were eligible for laser photocoagulation or for photodynamic therapy (PDT). These numbers highlight the deficiencies of current treatment modalities for exudative ARMD. For this reason, alternative treatment should be further investigated to offer better treatment to patients with exudative ARMD.