Blood-Aqueous Barrier Disruption in Penetrating and Posterior Lamellar Keratoplasty: Implications for Clinical Outcome. / Blut-Kammerwasser-Schranken-Störungen bei perforierender und posteriorer lamellärer Keratoplastik: Implikationen für das klinische Ergebnis.

BACKGROUND: The blood-aqueous barrier (BAB) separates immunoprivileged tissue of the eye from the blood circulation. Disruption of the BAB is therefore a risk factor for rejection after keratoplasty. PURPOSE: The present work provides a review of the work of our group and others on BAB disruption in penetrating and posterior lamellar keratoplasty and its implications for clinical outcome. METHODS: A PubMed literature search was performed to generate a review paper. RESULTS: Laser flare photometry provides an objective and reproducible method to assess the integrity of the BAB. Studies of the flare after penetrating and posterior lamellar keratoplasty demonstrate a mostly regressive disruption of the BAB in the postoperative course, which is influenced in extent and duration by multiple factors. Persistently elevated flare values or an increase in flare after initial postoperative regeneration may indicate an increased risk of rejection. DISCUSSION: In case of persistent or recurrent elevated flare values after keratoplasty, intensified (local) immunosuppression may potentially be useful. This could become important in the future, especially for the monitoring of patients after high-risk keratoplasty. Whether an increase of the laser flare is a reliable early indicator of an impending immune reaction after penetrating or posterior lamellar keratoplasty has to be shown in prospective studies.

Targeted Medical History and Diagnostic Testing in Uveitis. / Zielgerichtete Anamnese und Diagnostik bei Uveitis.

Uveitis is a collective term for a variety of different intraocular inflammations. The underlying etiologies vary greatly depending on the uveitis subtype, and in particular the anatomical focus. The most common forms of anterior uveitis are acute fibrinous unilateral uveitis, often associated with the HLA-B27 haplotype, and granulomatous inflammation, typically associated with sarcoidosis or herpes infections. Intermediate uveitis is usually idiopathic in nature but can also be associated with multiple sclerosis or sarcoidosis, while vitreoretinal lymphoma must also be considered as a masquerade syndrome in patients aged over 45. Posterior uveitis, on the other hand, as well as retinal vasculitis and panuveitis, have a very broad variety of etiologies; these can, however, be narrowed down through a similar findings-centered approach. Retinitis, for example, is often associated with infections (Toxoplasma gondii and viruses of the herpes group), whereas chorioditis is frequently idiopathic, although infections such as tuberculosis may occur. Therefore, the medical history and laboratory diagnosis should be tailored in patients with uveitis based on the anatomic focus of inflammation (anterior, intermediate, or posterior uveitis, or panuveitis) and the clinical picture (e.g., granulomatous versus nongranulomatous).

Ocular Involvement in COVID-19: Conjunctivitis and More. / Okuläre Mitbeteiligung bei COVID-19: Konjunktivitis und mehr.

Since the beginning of 2020, SARS-CoV-2, the pathogen of COVID-19, has led to a global pandemic that also affects ophthalmology. Ophthalmologists can be confronted at any time with potentially COVID-19 associated ocular symptoms or manifestations in patients and also become infected through close patient contact. Even without systemic infection, the ocular surface can come into direct contact with aerosols or liquids containing SARS-CoV-2 particles. A smear infection through hand-to-eye contact is also possible. A purely isolated ocular infection has not yet been shown. Rather, it seems that ocular complications occur in the context of a systemic infection. However, ocular symptoms can also be the first symptom of COVID-19. The most common ocular complication of COVID-19 is mild follicular conjunctivitis. Haemorrhagic conjunctivitis, dry eye disease, episcleritis, or retinal involvement can also occur less frequently. There are currently no evidence-based therapy recommendations for COVID-19 associated diseases of the ocular surface. Artificial tears might be helpful for symptom relief. There is no evidence for antiviral, antibiotic, or anti-inflammatory therapies, but these medications might be used in individual cases. Potential intraocular complications include retinal artery occlusions and haemorrhages, as well as cotton wool spots caused by complement-mediated thrombotic angiopathy. Neuro-ophthalmological complications including Miller-Fisher syndrome or infarct-related central blindness can also occur in very rare cases. Knowledge of potential transmission routes and personal protective equipment is just as essential for each ophthalmologist as a basic knowledge of potential ocular symptoms and complications.

No secret hiding place? Absence of SARS-CoV-2 on the ocular surface of 1145 hospitalized patients in a pandemic area.

OBJECTIVES: The aims of this study were to evaluate the isolated prevalence of real-time reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 on the ocular surface without systemic infection in hospitalized asymptomatic patients and to determine the risk for ophthalmologists and medical staff to be infected by prescreened asymptomatic patients in a tertiary eye care center. METHODS: In this prospective, observational study, bilateral swaps of the conjunctiva in the lower fornices as well as nasopharyngeal swaps were collected in 1145 hospitalized asymptomatic patients of a tertiary eye care center. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was performed for each swap to evaluate the prevalence of SARS-CoV-2. Demographic data and potential risk factors for an isolated infection of the ocular surface were noted. RESULTS: Two thousand two hundred eighty-eight (99.9%) of all 2290 tested eyes had negative results in the RT-PCR analysis of the conjunctival swabs. One patient had bilateral false-positive results in the conjunctival swabs. None of the 1145 patients had any positive RT-PCR-confirmed result in the nasopharyngeal swabs. CONCLUSIONS: The risk for an isolated conjunctival viral activity in patients with a negative nasopharyngeal swab-based RT-PCR seems to be absent or extremely low, suggesting no need to perform additional conjunctival swabs in patients with negative nasopharyngeal swabs. Furthermore, the risk of a work-related SARS-CoV-2 infection due to direct contact with preselected asymptomatic patients in an eye care center is very low, especially when additional hygiene standards and safe distances are respected carefully. This might reassure medical staff and reduce the fear of SARS-CoV-2 infection.

More than loss of taste and smell: burning watering eyes in coronavirus disease 2019.

OBJECTIVES: To evaluate ocular symptoms in European non-hospitalized patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and to investigate associations with the demographic data as well as nasal and general physical symptoms. METHODS: In this prospective, observational study, 108 non-hospitalized patients with PCR-confirmed SARS-CoV-2 infection not requiring intensive care were asked about disease-associated ocular symptoms, demographic data, as well as general physical and nasal symptoms using a standardized questionnaire. Total ocular symptom score (TOSS) was evaluated during and, retrospectively, before development of coronavirus disease 2019 (COVID-19). Associations between TOSS and demographic data as well as general and nasal symptoms were evaluated. RESULTS: Seventy-five of the 108 COVID-19 patients (69.4%) had at least one ocular symptom during COVID-19. The most common symptoms included burning sensations in 39 (36.1%), epiphora in 37 (34.3%) and redness in 28 (25.9%), compatible with conjunctivitis. These symptoms occurred 1.96 ± 3.17 days after the beginning of COVID-19 and were mild. TOSS was significantly higher during COVID-19 (1.27 ± 1.85) than before the infection (0.33 ± 1.04; p < 0.001). There were no significant associations between TOSS and gender (ß coefficient -0.108; p 0.302), age (-0.024; p 0.816), rhinorrhoea (-0.127; p 0.353), nasal itching (-0.026; p 0.803), sneezing (0.099; p 0.470), nasal congestion (-0.012; p 0.930), cough (-0.079; p 0.450), headache (0.102; p 0.325), sore throat (0.208; p 0.052), or fever (0.094; p 0.361). CONCLUSIONS: Ocular involvement in European non-hospitalized individuals with COVID-19 seems to be highly underestimated. Overall, these ocular symptoms, including burning sensations, epiphora and redness, seem to be mild and to not need treatment.

[The role of ophthalmology in the COVID-19 pandemic]. / Die Rolle der Augenheilkunde in der COVID-19-Pandemie.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 19 (COVID-19) has led to a worldwide pandemic. This pandemic presents a huge challenge for the healthcare system and also for ophthalmologists. Previous studies and case reports indicated that SARS-CoV­2 also infects the conjunctiva resulting in conjunctivitis. In addition, infectious virus particles in the tear fluid can be potential sources of infection; however, the detection of SARS-CoV­2 RNA in the tear fluid has rarely been successful. Although isolated conjunctival involvement is highly unlikely, at the current point in time of the COVID-19 pandemic, practically every patient examined by an ophthalmologist could be infected with SARS-CoV­2. Therefore, protective and hygiene measures should currently be consistently followed to minimize the risk of spreading the virus. Currently, there are no treatment recommendations for conjunctivitis associated with COVID-19. Tear substitutes might be helpful for symptom relief but there is no evidence for a topical antiviral therapy. In the future ophthalmologists could play a decisive role in the screening of maculopathies that might occur during COVID-19 treatment using chloroquine or hydroxychloroquine.

[Macular Oedema in Uveitis: Pathogenesis, Diagnosis, and Treatment]. / Makulaödem bei Uveitis: Pathogenese, Diagnostik und Therapie.

Macular oedema is the most common cause of irreversible visual loss in patients with uveitis. The pathogenesis is caused by pro-inflammatory cytokines that lead to the breakdown of the blood-retina barrier. For the diagnosis of inflammatory macular oedema, optical coherence tomography is now mainly used, but cannot always replace fluorescein angiography. The therapy is mainly performed with intravitreally applied corticosteroids as well as systemic immunomodulators and should start as early as possible to prevent chronification of macular oedema.

Perceived Stress Levels in Adult Patients With Uveitis.

Background: The aim of this study was to examine perceived stress levels in adult patients with uveitis. Patients and Methods: One hundred seventy-three adult consecutive uveitis patients (age range 18 to 85 years) were analyzed in a cross-sectional design for their perceived stress, according to the Perceived Stress Questionnaire (PSQ). Stress levels were classified into normal stress, moderate stress, and high stress. Results: In the majority of uveitis patients a normal stress level (82%) within the last 2 years was detected. In a subgroup analysis, perceived stress of the patients with active uveitis compared with patients with non-active uveitis was significantly higher within the last 2 years (n=80 active/n = 45 non-active; p = 0.005). Conclusions: Overall 18% of the uveitis patient had raised perceived stress, similar to the general population but patients with active uveitis were significantly more stressed. Therefore, consideration of stress levels may be important in the therapy of uveitis patients.

The Phenotype of Monocytes in Anterior Uveitis Depends on the HLA-B27 Status.

HLA-B27 is the allele most frequently associated with human anterior uveitis. The majority of HLA-B27-positive [acute anterior uveitis (AAU)] patients develop clinically distinct symptoms with acute symptomatic onset of flare and a recurrent disease course characterized by a massive cellular ocular infiltrate during uveitis relapse. By contrast, uveitis in HLA-B27-negative [idiopathic anterior uveitis (IAU)] patients tends to develop a clinically less fulminant, more chronic, and typically asymptomatic disease course. To analyze systemic immune responses in the different uveitis entities, we analyzed peripheral blood cells by flow cytometry. In addition, as a pro-inflammatory biomarker serum, S100A8/A9 levels were quantified by ELISA from patients with AAU (n = 27) and IAU (n = 21), and in healthy controls (n = 30). Data were obtained either during active uveitis flare or after 3 months of inactivity. IAU patients showed a transiently increased frequency of CD56- and CD163-positive monocytes and of both granulocytic myeloid-derived suppressor cells and Th17 cells during active uveitis. By contrast, AAU patients showed an elevated frequency of monocytes, activated T cells, and elevated S100A8/A9 serum levels during clinically quiescent disease. The differentially regulated response of both innate and adaptive immune cells in the blood may be related to the clinically distinct characteristics of the two different uveitis entities.

Analysis of the impact of allergy and atopy on new onset of uveitis.

PURPOSE: The inappropriate immune response to harmless foreign and self-antigens is a common feature of allergy, atopy and autoimmune disease. The influence of environmental factors in the initiation of autoimmunity is not well understood. It is conceivable that immune responses to allergens may also serve as a trigger of bystander immune reactions, including autoimmunity such as uveitis. Therefore, we wanted to investigate the prevalence of allergies and atopy in patients with different types of uveitis in comparison to a control cohort. METHODS: In total, 530 consecutive patients with new-onset anterior, intermediate, posterior and panuveitis were compared to a non-uveitis control cohort consisting of 1.060 consecutive new-referral patients who attended our specialized outpatient clinics for other reasons than uveitis. Allergy and atopy status as well as demographic data (age, gender and ethnicity) were obtained by standardized interviewer-assisted questionnaires. RESULTS: Uveitis case cohort and control cohort did not differ significantly in the allergy status (p = 0.910), such as the history of pollen allergy (p = 0.671), history of drug allergy (p = 0.920), history of food allergy (p = 0.941), history of house dust mite allergy (p = 0.197) or history of other allergens (p = 0.593), nor in the atopy status (p = 0.802), such as the history of atopic dermatitis (p = 0.365), history of asthma (p = 0.430) or history of allergic rhinitis (p = 0.115). CONCLUSIONS: Our results argue against a substantial influence of allergies and atopy on the onset of uveitis.

Impact of allergy and atopy on the risk of pseudophakic cystoid macular edema.

PURPOSE: To assess the risk of pseudophakic cystoid macular edema (PCME) following cataract surgery in patients with allergies and/or atopic disorders. PATIENTS AND METHODS: Medical records of 3,850 consecutive eyes that underwent cataract surgery were retrospectively reviewed for prevalence of allergies and atopic status and development of PCME. Patients with any known risk factors for PCME were excluded. Macular examination was performed using spectral-domain optical coherence tomography (SD-OCT) before and at 4, 8, 12, 16, 24, and 36 weeks after surgery. If both eyes in one patient underwent cataract surgery, one eye was randomly selected. Odds ratios and confidence intervals were estimated. RESULTS: Out of 240 patients enrolled in this series, 65 patients (27.1 %) showed positive allergic status, 19 patients (7.9 %) suffered from atopic syndromes, and 11 (4.6 %) showed both (allergies and atopic diseases). PCME occurred in eight patients (12.3 %) of the allergy cohort, whereas no patient (0 %) of the atopy cohort developed PCME. The risk of PCME was comparable in patients with allergies or atopic diseases to patients without allergies or atopy (allergy: p = 0.635; odds ratio (OR) 1.303, 95 % confidence interval (CI) 0.461-3.398; atopy: p = 0.234; OR 0.000, 95 % CI 0-1.815). CONCLUSION: Positive status of allergy or atopy does not seem to increase the risk of PCME. Therefore, postoperative treatment after cataract surgery does not have to be modified in allergic or atopic patients.

Cataract in pseudohypoparathyroidism.

UNLABELLED: A 22-year-old white man presented with photopsia of 3-year duration despite a corrected distance visual acuity of 20/20 in both eyes. Ophthalmic examination revealed multiple irregularly shaped white cortical opacifications of the lens in both eyes but no other significant ocular findings. One year after the photopsia onset, the patient experienced an episode of seizures with generalized tonic-clonic movements. Neurological follow-up examination demonstrated extensive brain calcification in the basal ganglia and frontal lobes, leading to a diagnosis of pseudohypoparathyroidism. Pseudohypoparathyroidism is a rare condition, and there are few reports of ocular findings with this underlying pathology. Our findings clearly demonstrate that even relatively unremarkable ocular signs can lead to diagnosis of severe systemic diseases. Therefore, the cataract surgeon should be aware of these conditions before removing the lens. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

The Trojan Horse Tale Revisited: An Eye on Metastatic Spread of Carcinoma Cells.

The metastatic spread of carcinoma cells is not fully understood. Here, we compare the peripheral blood mononuclear cells (PBMC) and intraocular metastatic cells in parotid gland carcinoma with the PBMCs of healthy donors by immunohistochemistry and flow cytometry. We found Ber-EP4 tumor marker-positive carcinoma cells in the aqueous humor of the patient's right eye and a CD45 and Ber-EP4-expressing PBMC population in his blood. These Ber-EP4-expressing cells exhibited a monocytic-myeloid phenotype with coexpression of CD11b, CD115, and the macrophage marker CD172a (SIRP-α). Uptake of pHrodogreen revealed their phagocytic activity. Our findings suggest that the tumor cells in the anterior chamber originally derived from cell fusions between tumor cells and myeloid cells in the peripheral blood. Thus, metastases of a solid malignancy could use monocytes-macrophages as the Trojan horse to enter the eye.

Spectrum of Uveitis in A German Tertiary Center: Review of 474 Consecutive Patients.

PURPOSE: To analyze the spectrum of uveitis at a German tertiary center. PATIENTS AND METHODS: A total of 474 consecutive patients with uveitis were classified according to the primary anatomic site of inflammation, examined for laterality of disease, and screened for etiologies. RESULTS: Out of the total, 253 patients (53%) had anterior uveitis, 90 patients (19%) had intermediate uveitis, 100 patients (21%) had posterior uveitis, and 31 patients (7%) had panuveitis. Fifty-six percent of the patients had bilateral involvement, predominantly in intermediate uveitis (ratio 4:1) and panuveitis (ratio 3.4:1). Regarding the etiology of all uveitis cases we found 17% infectious, 23% specific clinical entities, 20% associated with systemic disease (most commonly sarcoidosis with 11%), and 41% idiopathic uveitis. CONCLUSIONS: Anterior uveitis was the most common anatomic site of intraocular inflammation. Using a tailored approach, screening for systemic etiologies is recommended, since 20% of all patients had associated systemic diseases.