Eye Disease in Patients with Rheumatic Diseases: A Retrospective Observational Cohort Study.

Data on eye diseases in rheumatic patients are limited. The aim of this study was to retrospectively assess the prevalence of ophthalmologic diseases in patients at a rheumatology outpatient clinic who also visited the ophthalmologic clinic. For this retrospective observational cohort study, a chart review was performed according to the STROBE guidelines. In this cohort, an ophthalmologic diagnosis was made in 26.9% of the 1529 rheumatic outpatients, whereas from a rheumatologic perspective, inflammatory non-infectious diagnoses dominated, at 71.7%. From an ophthalmologic perspective, diagnoses without inflammatory pathophysiologic backgrounds dominated, at 54.9%. Inflammatory non-infectious ophthalmologic disease was diagnosed in 24.2% of patients with rheumatoid arthritis and 29.3% of patients with peripheral spondyloarthritis. Not a single rheumatoid arthritis patient was diagnosed with anterior uveitis; however, 16.5% of spondyloarthritis patients were diagnosed with anterior uveitis (p < 0.001). The prevalence of uveitis was 16.3% in axial and 20.1% in peripheral spondyloarthritis. In conclusion, an interdisciplinary rheumatologic-ophthalmologic setting appears justified to further improve the management of patients with rheumatic diseases.

Symptomatic idiopathic bilateral multifocal retinal pigment epithelial detachments.

PURPOSE: To report a rare case of idiopathic bilateral serous retinal pigment epithelial detachments. OBSERVATIONS: We present a case of a 43-year-old female patient with metamorphopsia with the presence of innumerable bilateral serous retinal pigment epithelial detachments. Detailed ocular and systemic clinical work-up revealed no underlying disease. CONCLUSIONS: /Importance: Idiopathic multiple serous retinal pigment epithelial detachments are an extremely rare condition, that has been observed as an incidental clinical finding in asymptomatic patients. Multimodal imaging and detailed systemic work up are essential to rule out an underlying disease. Initial symptoms, as in our case, are uncommon and usually occur only in patients with complications such as choroidal neovascularization or hemorrhages. Therefore, regular follow ups are recommended to early detect and treat possible complications.

Two Cases of Acute Macular Neuroretinopathy Associated with the Adenovirus-based COVID-19 Vaccine Vaxzevria (Astrazeneca).

PURPOSE: To report two cases of acute macular neuroretinopathy (AMN) in young female patients following the administration of the adenovirus-based coronavirus disease 2019 (COVID-19) vaccine Vaxzevria (AstraZeneca). METHODS: Spectral-domain optical coherence tomography and infrared imaging were used to confirm the diagnosis of AMN. RESULTS: Both patients showed a parafoveal hyperreflective band in the outer nuclear layer, disruption of the ellipsoid and interdigitation zones of the photoreceptor layers, and correlating hyporeflective areas on the near-infrared images. Both patients presented with flu-like fever and sudden onset of fortifications within 48 hours of vaccination. One patient showed altered flow in the deep capillary plexus and highly elevated thrombotic parameters. CONCLUSION: We report a possible association between immune-mediated AMN and the administration of adenovirus-based COVID-19 vaccine Vaxzevria.

Uveitis in Tumor Patients Treated with Immunological Checkpoint- and Signal Transduction Pathway-Inhibitors.

PURPOSE: New tumor therapies like immune checkpoint inhibitors and small molecule inhibitors of MEK and BRAF have increased the patient's survival rate but can be burdened with severe side-effects including uveitis. Here, we show the spectrum, treatment, and outcome of uveitis types induced by tumor treatment. METHODS: In this retrospective study, we have included 54 patients from different centers who were developing uveitis under tumor therapy. A 16-item questionnaire was analyzed for type, treatment, and outcome of uveitis and type of tumor treatment, which we have correlated here. RESULTS: Irrespective of the tumor treatment, most patients developed anterior uveitis. All patients received corticosteroids and some additional immunosuppressive treatments. Cessation of tumor therapy was necessary only in a minority of cases. CONCLUSIONS: Ocular autoimmunity should be differentiated from toxic effects of cancer treatment and timely recognized since it can be generally well controlled by anti-inflammatory treatment, preserving the patient's vision without cessation of the tumor treatment.

Effects of COVID-19 protective measures on the ophthalmological patient examination with an emphasis on gender-specific differences.

OBJECTIVE: In response to the COVID-19 pandemic, strict hygiene and containment measures have been instituted in the clinical ophthalmological examination to prevent virus transmission. The aim of this study is to assess the effects of these protective measures on the quality of the examination with an emphasis on gender-specific differences. METHODS AND ANALYSIS: An online survey was sent to ophthalmologists in 10 countries. The collected data included demographics, place of work, current professional status, COVID-19 protective measures and their impact on the quality of the examination. Descriptive statistics were used to analyse the data. Fisher's exact test was used to analyse gender differences. RESULTS: A total of 120 responses were collected. 54.0% of the respondents identified as female and 43.4% as male. Over 75% agreed that protective measures made the examination conditions more difficult. The major problems were fogging of the lenses (87.6%) or slit lamp oculars (69.9%), reduced operability of the slit lamp due to protective barriers (60.2%) and time delay due to disinfection measures (68.1%). Significantly more women than men reported that they used filtering face piece (FFP2) instead of surgical masks (p=0.02). More male participants reported that they removed their mask to prevent fogging (p=0.01). 31% of all participants felt that the COVID-19 protective measures reduced the overall quality of slit lamp examination and 43.4% reported a reduced quality of fundoscopic examination. CONCLUSION: COVID-19 related safety measures reduce the feasibility of the clinical ophthalmological examination. Practicable solutions are required to maintain good examination quality without compromising personal safety.

Indocyanine Green Angiographic Assessment of Conjunctival Melanocytic Disorders.

PURPOSE: To investigate whether transvascular indocyanine green (ICG) dye leakage is associated with conjunctival malignancy. METHODS: This is a prospective interventional study. Patients presenting with circumscribed conjunctival melanocytic disorders (CMDs) were included and examined using color photography, anterior segment optical coherence tomography to measure lesion size, and fluorescein and ICG angiography to measure vascular pattern and leakage. Time to vascular leakage was measured by 2 independent observers. Lesions were characterized as benign or malignant based on histopathological features. RESULTS: Thirty patients with CMD were included: 22 lesions were benign (conjunctival nevus, n = 20; conjunctival melanocytic intraepithelial neoplasia without atypia, n = 2) and 8 were malignant (in situ conjunctival melanoma n = 2; invasive conjunctival melanoma, n = 6). Malignant lesions had larger mean maximal diameters (11.0 ± 4.5 vs. 4.2 ± 2.5 mm, P = 0.003) and more frequently showed intrinsic tumor vasculature (8 of 8 vs. 10 of 22, P = 0.007). The mean time to ICG leakage was 350.9 ± 165.9 seconds in benign and 59.6 ± 22.1 seconds (P = 0.002) in malignant lesions and was inversely correlated with lesion size and thickness. CONCLUSIONS: Time to angiographic ICG dye leakage is significantly shorter in malignant versus benign CMD.

Proton beam radiation for iris melanoma: case series and review of literature.

OBJECTIVE: Purpose of this study is to analyse the visual outcomes, the complication and eye retention rate as well as tumour control data of patients treated with proton beam radiation therapy (PBRT) for iris melanoma. METHODS: Retrospective case series and review based on patients' records. All tumours were categorised according to the American Joint Committee of Cancer staging criteria for primary iris melanoma und underwent either sectorial or whole anterior segment PBRT. RESULTS: Thirteen cases were identified of which five received PBRT of the whole anterior segment and eight received sectorial PBRT. Local tumour control after a mean follow-up of 25 months was 92%. Complications after PBRT included cataract (46%), secondary glaucoma (31%), superficial keratitis (15%) and madarosis (8%). Complications were more common in patients necessitating irradiation of the entire anterior segment than in patients which received sectorial irradiation. Eye retention was achieved in all cases. No statistically significant difference in the mean best corrected visual acuity (BCVA) and intraocular pressure (IOP) was found before and after treatment. Comparison of mean BCVA and IOP between different treatment groups (complete anterior segment vs sectorial irradiation) at the last follow-up visit were also not significantly different. No patient developed metastatic disease during follow-up. CONCLUSION: PBRT is a safe and vision preserving therapeutic modality for iris melanoma. Complete irradiation of the anterior segment is associated with higher complication rates.

Observation of angiographic dye leakage in ocular surface squamous neoplasia.

PURPOSE: The clinical diagnosis of ocular surface squamous neoplasia is challenging, mostly requiring excisional biopsy. Human tumor angiogenesis is characterized by abnormal vessel architecture and transvascular hyperpermeability. This case report describes features of fluorescein and indocyanine green angiography in a case of conjunctival intraepithelial neoplasia. OBSERVATIONS: Color photography, optical coherence tomography, fluorescein and indocyanine green angiography were performed in a patient with suspected conjunctival intraepithelial neoplasia before excisional biopsy and histologic confirmation of clinical diagnosis. Fluorescein dye showed extensive early extravascular dye leakage within the limits of the lesion. Indocyanine green dye displayed corneal terminal vessel bulbs with early leakage after 70 seconds and showed diffuse intralesional dye leakage after 7 minutes. CONCLUSIONS: Increased fluorescein and early indocyanine green dye leakage can be used to confirm active angiogenesis already in early stages of dysplastic ocular surface squamous neoplasia. Late leakage of indocyanine green dye may be due to chronic transvascular hyperpermeability within intrinsic tumor vessels. The leakage behaviour of intravenous dyes has the potential to serve as a diagnostic indicator of active growth in dysplastic ocular surface neoplastic lesions.

Ultra-wide-field imaging of choroidal melanoma before and after proton beam radiation therapy.

OBJECTIVE: To evaluate the imaging characteristics of choroidal melanoma before and after proton beam radiotherapy via Optos® ultra-wide-field scanning laser ophthalmoscopy. METHODS: Retrospective, descriptive study of choroidal melanoma patients treated with proton beam radiotherapy. All patients underwent full clinical evaluation, including best-corrected visual acuity, ultrasound examination and ultra-wide-field scanning laser ophthalmoscopy imaging in the pseudo-colour (red and green channel) as well as auto-fluorescence mode. Tumours were classified and evaluated according to their location, size, presence of subretinal fluid, drusen, orange pigment and reflectance intensity in ultra-wide-field scanning laser ophthalmoscopy. Tumour sonographic (basal diameter, height) and ultra-wide-field scanning laser ophthalmoscopy imaging dimensions (maximal diameter) were documented. RESULTS: A total of 39 eyes (38 patients) were followed for 24 months (range 6-48 months). Mean best-corrected visual acuity dropped from 20/40 to 20/63 after proton beam radiotherapy. There was no change in the imaging tumour characteristics during follow-up. Subretinal fluid changes were better detected in the autofluorescence compared to pseudo-colour mode. Mean tumour diameter did not significantly change in the ultra-wide-field scanning laser ophthalmoscopy although it did so in the ultrasound. No patient showed local tumour recurrence. CONCLUSION: The ultra-wide-field scanning laser ophthalmoscopy imaging characteristics of choroidal melanoma in the Optos® system do not significantly change after proton beam radiotherapy after a mean follow-up of 2 years.

[Patient Mobility and Journey Distance as Risk Factors for Severe Visual Impairment: Real-Life Data Analysis of Treatment-naïve Patients with nAMD under Intravitreal Aflibercept Therapy]. / PatientInnen-Mobilität und Anreisedistanz als Risiko für höhergradige Sehbehinderung: Real-Life-Daten therapienaiver AMD-PatientInnen unter intravitrealer Aflibercept-Therapie.

OBJECTIVE: The aim of this study is to describe the effectiveness of aflibercept in treatment-naive patients with neovascular age related macular degeneration (nAMD) and the impact of patients' residential distance to the clinic and patients' mobility on therapy in a pro re nata regime. METHODS: A retrospective dataset analysis of 483 treatment-naive patients with nAMD was performed. The main outcomes were best corrected visual acuity (BCVA), central foveal thickness (CFT), bilateral visual impairment, distance and type of transport to the clinic. Secondary outcomes were injection rate, numbers and reasons of loss to follow-up. RESULTS: Patients received 4.91 ± 1.9 injections in their first year and 7.06 ± 3.6 after the period of 25 months (m). Initially the BCVA improved significantly after a loading dose from 0.72 logMAR (± 0.44) to 0.63 logMAR (± 0.45; p = 0.03). However, the BCVA significantly decreased after 2 years to 0.82 (± 0.48; p < 0.001). The proportion of patients with higher visual impairment and patients needing assistance with transport increased with the distance of their residence to the clinic (both p < 0.001). The LTFU rate was 3% and showed a correlation with greater age (p = 0.019). CONCLUSION: The presented data show that aflibercept is effective for the treatment of nAMD. Although a good increase in visual acuity is initially achieved in the majority of patients, the initial success of treatment is not maintained throughout the course of the disease. Compared to controlled clinical studies, the presented data show reduced therapeutic success and lower injection frequencies. The rising demand for patient transport aid and increased visual impairment with increased distance indicate potential problems within the healthcare system.

C-Shaped Scotoma after Complicated Cesarean Section: A Case of Acute Macular Neuroretinopathy.

Acute macular neuroretinopathy (AMN) is a rare retinal disease that produces transient or permanent visual impairment and occurs predominantly in young, Caucasian women of childbearing age. It is often characterized by wedge-like macular lesions. Although the cause of AMN is unknown, recent research suggests a microvascular etiology. Various vascular pathologies, including post-viral illness, oral contraceptives, and use of vasoconstrictive agents, have been associated with AMN. We present a case of a woman with C-shaped visual field defects in both eyes after inadvertent exposure to intravenous high-dose epinephrine during onset of spinal anesthesia. At present, only 8 cases of AMN after exposure to epinephrine have been described in literature. To our knowledge, this is the first case of AMN that presented following epinephrine injection during childbirth.

The involvement of NK1 and Y2 receptor in the development of laser-induced CNVs in C57Bl/6N mice.

PURPOSE: to explore whether the NK1 and Y2 receptors are involved in the pathogenesis of laser-induced CNV (choroidal neovascularization) in C57Bl/6N mice. METHODS: CNV was induced by laser damage of Bruch's membrane and the CNV volume was determined by OCT and/or flatmount preparation. First, the development of the CNV volume over time was evaluated. Second, the CNV development in NK1- and Y2 KO mice was analyzed. Third, the effect on the development as well as the regression of CNV by intravitreal injections of the NK1 antagonist SR140333 and the Y2 antagonist BIIEO246 separately and each in combination with Eylea®, was investigated. Furthermore, flatmount CNV volume measurements were correlated to volumes obtained by the in vivo OCT technique. RESULTS: CNV volume peak was observed at day 4 after laser treatment. Compared to wild type mice, NK1 and Y2 KO mice showed significantly smaller CNV volumes. Eylea® and the Y2 antagonist significantly reduced the volume of the developing CNV. In contrast to Eylea® there was no effect of either antagonist on the regression of CNV, additionally no additive effect upon combined Eylea®/antagonist treatment was observed. There was a strong positive correlation between CNV volumes obtained by OCT and flatmount. CONCLUSION: NK1 and Y2 receptors mediate the development of laser-induced CNVs in mice. They seem to play an important role at the developmental stage of CNVs, whereas VEGF via VEGF receptor may be an important mediator throughout the CNV existence. In vivo OCT correlates with flatmount CNV volume, representing a useful tool for in vivo evaluations of CNV over time.

[Surgical Methods in the Treatment of Uveal Melanoma]. / Chirurgische Methoden in der Behandlung des Aderhautmelanoms.

Significant advancements have been made in the last decades in the treatment of uveal melanoma. Radiation therapy can achieve, depending on the method, local tumour control in up to 98% of cases. Surgical modalities have been implemented in the ocular therapy for uveal melanoma either to treat/prevent radiation complications, such as so-called toxic tumour syndrome, or to primarily treat the tumour with or without adjunctive radiotherapy. These include endoresection and transscleral resection for melanomas of the choroid/ciliary body or irido-trabeculo-cyclectomy for melanomas of the iris-ciliary body. Furthermore, tumour biopsy is playing a progressively more important role in the diagnosis, treatment and follow-up planning of melanoma cases. This paper focuses on the background, the surgical technique as well as the results and complications of tumour excisional and biopsy surgery.

Severe reactive ischemic posterior segment inflammation in Acanthamoeba keratitis: Case report of a patient with Sjögren's syndrome.

PURPOSE: We report on a case of Acanthamoeba keratitis (AK)-related reactive ischemic posterior segment inflammation following intraocular surgery in a patient with primary Sjögren's syndrome (PSS). CASE REPORT: A 48-year-old female patient with severe protracted AK underwent uneventful cataract surgery upon development of a corneal scar. Four weeks postoperatively, she experienced a rapid loss of vision to no light perception. Central retinal artery occlusion and ischemic optic neuropathy could be excluded, and a diagnosis of PSS was made. The condition remained unresponsive to systemic steroid treatment and ultimately led to enucleation of the globe. Histologic work-up revealed ischemic posterior segment inflammation and Acanthamoeba cysts in the corneal stroma. CONCLUSION: Autoimmune disease may be a risk factor for AK-related severe reactive ischemic posterior segment inflammation, and intraocular surgery can be a trigger to its manifestation.

Decreased Vision as Initial Presenting Symptom of Acute Lymphoblastic Leukemia: A Case Report.

This case illustrates that hematologic disorders must be considered as a potentially life-threatening cause for vision loss. Proper laboratory workup and timely interdisciplinary approach are essential to ensure the best possible care for ophthalmic patients. Historically, before the use of bone marrow biopsy, the ophthalmologist was often asked to assist in the diagnosis of leukemia. Since ophthalmological symptoms may be the initial presenting signs of leukemia as highlighted in this case, the ophthalmogist is still of crucial importance.

Reduced-fluence photodynamic therapy combined with ranibizumab for nonproliferative macular telangiectasia type 2.

PURPOSE: To report the efficacy of reduced-fluence photodynamic therapy (PDT) combined with intravitreal ranibizumab for the treatment of nonproliferative macular telangiectasia (MacTel) type 2. METHODS: Noncomparative, interventional, retrospective case series; 5 eyes of 4 patients were studied. Patients were treated with reduced-fluence PDT and intravitreal ranibizumab within 24 h. After initial treatment, follow-up was at least 12 months in all patients. RESULTS: At baseline median logMAR (logarithm of the minimal angle of resolution) best-corrected visual acuity (BCVA) was 1.0 (range, 1.0-0.3). At 3 months of follow-up vision increased in 3 out of 5 eyes and median BCVA was 0.4 (range, 1.0-0.2). The gain of BCVA ranged from 6 lines to 1 line. Visual acuity remained stable in the other 2 study eyes. No eyes lost vision at 3 months of follow-up. At 12 months of follow-up median logMAR BCVA was 0.7 (range, 1.3-0.3). Two eyes had maintained their gain in BCVA compared to baseline. Two eyes lost vision compared to baseline and 1 eye showed unchanged visual acuity at 12 months of follow-up. CONCLUSION: A combination therapy with reduced-fluence PDT and intravitreal ranibizumab might be a valuable treatment option for eyes with progressive vision loss due to nonproliferative MacTel type 2.

PE-11, a peptide derived from chromogranin B, in the rat eye.

The aim of the study was to investigate the presence and distribution of PE-11, a peptide derived from chromogranin B, in the rat eye. For this purpose, newborn rats were injected with a single dosage of 50mg/kg capsaicin subcutaneously under the neck fold and after three months, particular eye tissues were dissected and the concentration of PE-11-like immunoreactivity was determined by radioimmunoassay. Furthermore, PE-11-like immunoreactivities were characterized in an extract of the rat eye by reversed phase HPLC. Then, the distribution pattern of PE-11 was investigated in the rat eye and rat trigeminal ganglion by immunofluorescence. As a result, PE-11 was present in each tissue of the rat eye and capsaicin pretreatment led to a 88.05% (±7.07) and a 64.26% (±14.17) decrease of the levels of PE-11 in the cornea and choroid/sclera, respectively, and to a complete loss in the iris/ciliary body complex. Approximately 70% of immunoreactivities detected by the PE-11 antiserum have been found to represent authentic PE-11. Sparse nerve fibers were visualized in the corneal and uveal stroma, surrounding blood vessels at the limbus, ciliary body and choroid and in association with the dilator and sphincter muscle. Furthermore, immunoreactivity was present in the corneal endothelium. In the retina and optic nerve, glia was labeled. In the rat trigeminal ganglion, PE-11-immunoreactivity was visualized in small and medium sized ganglion cells with a diameter of up to 30µm. In conclusion, there is unequivocal evidence that PE-11 is a constituent of capsaicin-sensitive sensory neurons innervating the rat eye and the distribution pattern is typically peptidergic in the peripheral innervation but in the retina completely atypical for neuropeptides and unique.

Involvement of protein kinase C in phagocytosis of human retinal pigment epithelial cells and induction of matrix metalloproteinase secretion.

Protein kinase C (PKC) is involved in cell activation. We investigated PKC-mediated pathways and secretion of matrix metalloproteinases (MMPs) in phagocytosis by human retinal pigment epithelial cells (RPE). We used time-resolved fluorometry for europium-labeled microsphere uptake and gel zymography to assay the influence of PKC modulators. PKC inhibitors blocked phagocytosis by RPE. ARPE-19, a human RPE-cell line, showed reduced secretion of MMP-2, although MMP-9 secretion by PKC activation was conserved in both cell types, namely in the primary RPEs and in the RPE-cell line. Particle uptake by RPE cells requires activation of PKC; the use of PKC inhibitors as new anticancer drugs may possibly cause ocular side-effects.