Detection of Scedosporium spp.: Colonizer or pathogen? A retrospective analysis of clinical significance and management in a large tertiary center.

Infections with Scedosporium spp. are emerging in the past two decades and are associated with a high mortality rate. Microbiological detection can be associated with either colonization or infection. Evolution from colonization into infection is difficult to predict and clinical management upon microbiological detection is complex. Microbiological samples from 2015 to 2021 were retrospectively analyzed in a single tertiary care center. Classification into colonization or infection was performed upon first microbiological detection. Clinical evolution was observed until July 2023. Further diagnostic procedures after initial detection were analyzed. Among 38 patients with microbiological detection of Scedosporium spp., 10 were diagnosed with an infection at the initial detection and two progressed from colonization to infection during the observation time. The main sites of infection were lung (5/12; 41.6%) followed by ocular sites (4/12; 33.3%). Imaging, bronchoscopy or biopsies upon detection were performed in a minority of patients. Overall mortality rate was similar in both groups initially classified as colonization or infection [30.7% and 33.3%, respectively (P = 1.0)]. In all patients where surgical debridement of site of infection was performed (5/12; 42%); no death was observed. Although death occurred more often in the group without eradication (3/4; 75%) compared with the group with successful eradication (1/8; 12.5%), statistical significance could not be reached (P = 0.053). As therapeutic management directly impacts patients' outcome, a multidisciplinary approach upon microbiological detection of Scedosporium spp. should be encouraged. Data from larger cohorts are warranted in order to analyze contributing factors favoring the evolution from colonization into infection.

Scedosporium is an environmental mould with a varied clinical relevance, as described in this cohort from a tertiary centre. Its microbiological detection represents a colonization or infection. An interdisciplinary approach is crucial for an optimal diagnostic strategy and patient outcome.

A Novel Technique of Aseptic Manufacture of Autologous Serum Eye Drops (ASEDs) and Sterility Analysis of the Bottled Ophtioles.

PURPOSE: To introduce a novel technique of the aseptic manufacture of autologous serum eye drops (ASEDs) with a prefiltered closed system and to analyze the sterility of the produced ophtioles between 2018 and 2022. METHODS: This is a prospective single-center study conducted at the Department of Ophthalmology at a Swiss University Hospital between 2018 and 2022. For regulatory reasons, closed systems for manufacturing ASEDs are strongly recommended. We attached an upstream sterile filter (Sterivex PES0.22 µm Burlington, USA) to a commercially available closed system (COL System Modena, Italy) for manufacturing ASEDs. The goal of this novel approach was to reduce the microbiological contamination of the donated autologous blood. Using the presented manufacturing method, we are able to produce, on average, 56 ophtioles per batch, containing either 1.45 mL or 2.5 mL of autologous serum per ophtiole. For each batch of ASEDs, we performed a microbiological analysis by automated blood culture testing (BACTEC). This system examines the presence of bacteria and fungi. RESULTS: We analyzed all manufactured batches between 2018 and 2022. None of the 2297 batches and the resulting 129 060 ophtioles showed bacterial or mycotic contamination. During the analyzed period, two batches were discarded: one due to fibrin-lipid aggregations, further microbiological and histological work-up excluded any contamination; another due to false-positive HIV in serological testing. Overall, the contamination rate was 0%, and the batch discharge rate was 0.09%. CONCLUSIONS: The combination of upstream sterile filtration with a commercial closed system for manufacturing ASEDs proved to be effective in ensuring sterility without any contamination over the past 4 years. This is becoming crucial, as the demand for autologous blood products for treating ocular surface disorders, such as refractory dry eyes or nonhealing defects of the corneal epithelium, is on the rise.

National Consensus on Contraindications for Corneal Donation for Transplantation in Switzerland.

PURPOSE: To establish a national consensus on contraindications for corneal donation for transplantation in Switzerland. METHODS: Swisstransplant (SWT), the Swiss national foundation coordinating tissue and organ donations, convened a working group consisting of six national corneal surgeons and eye bankers and donation experts to create a contraindication list for corneal donation. The group reviewed available national and international guidelines and recommendations, while adhering to Swiss law and transplant regulations. In cases of opposing opinions, the group held follow-up meetings until a consensus was reached. A consensus was defined as agreement among all parties present. RESULTS: From March 2021 to November 2021, the study group held six meetings and created a standardized minimal contraindication list for corneal donation in Switzerland. Thanks to this list, SWT has created a mandatory working and documentation file for donor coordinators to use when evaluating multiorgan donors for corneal harvesting. The authors agreed that while the national consensus list provides standardized minimal contraindication criteria, local eye banks may choose to introduce additional, more rigorous criteria. CONCLUSION: Given that corneal transplantation is the most commonly performed transplantation, establishing a consensus on contraindications is crucial for recipient safety. The creation of a consensus on contraindications for corneal donation in Switzerland is an essential contribution to fulfil the legal requirements concerning quality assurance and provides sufficient high-quality donor tissue within the country. Therefore, periodic review and revision of the consensus is considered critical.

Evaluation of Increase in Retinal Thickness as Diagnostic Marker in Central Artery Occlusion.

PURPOSE: To evaluate the increase in retinal thickness as a marker in predicting the onset of central retinal artery occlusions. METHODS: Retrospective clinical study conducted at one Swiss hospital. Electronic records were filtered for patients with artery occlusions. Optical coherence tomography data, including time between the imaging and ischemic event, were reviewed. Increase in relative retinal thickness was measured, defined as an increase in retinal thickness compared to the unaffected partner eye. This was correlated with the time from symptom onset. A cutoff value of relative increase of < 24.5% was applied, as suggested in previous studies. The results were compared to the time gathered from the electronic records, and sensitivity, specificity, positive predictive value as well as negative predictive value were calculated for predicting an ischemia time of < 4.5 h. RESULTS: Forty-two eyes from 41 patients with central artery occlusions were identified. Fourteen were female. Mean age was 66.4 ± 15.8 years. Initial corrected visual acuity was 2.41 ± 0.68 logMAR, and 2.13 ± 0.87 logMAR at the last follow-up (p > 0.05). Of eyes with a visual acuity of counting fingers (n = 38) or worse, 89.5% showed no improvement during follow-up, while eyes with logMAR 1 or better (n = 4) improved. Thirteen eyes (13 patients) presented within 4.5 h of the ischemic event. Four patients received i. v. thrombolysis, with visual recovery in one. In 12 eyes with an ischemia time of < 4.5 h, relative increase was below 24.5%. In the remaining 29 eyes with > 4.5 h, relative increase was below 24.5% in 4 eyes and above 24.5% in 25 eyes. This yielded a sensitivity of 92.3%, a specificity of 86.2%, with a positive predictive value of 75.0% and a negative predictive value of 96.2%. CONCLUSION: Central retinal artery occlusion is associated with severe vision loss. There is no current established therapy. Parameters that objectify the presence of a therapeutic window for thrombolysis are gaining in importance as patient history is often imprecise. Relative retinal thickness increase proved a noninvasive imaging parameter demonstrating adequate performance in detecting patients within the therapeutic window of thrombolysis. Further investigation of this parameter in central retinal occlusion is warranted.

Ophthalmological Outcomes in Patients with Susac Syndrome.

BACKGROUND: To report ophthalmological outcomes and treatment regimen in patients with Susac syndrome. METHODS: This is a retrospective analysis of patients with Susac syndrome treated between November 2015 and March 2023. Multimodal imaging findings, ophthalmic examination data, information on neurological and sensorineural involvement, and therapeutic regimen were reviewed. Visual acuity was recorded as the logarithm of the minimum angle of resolution (logMAR). Ophthalmological manifestations and disease severity were assessed using the previously described clinical activity score (CAS). RESULTS: Ten patients with Susac syndrome m : f = 5 : 5 were identified. The mean follow-up time was 31.2 ± 23.3 months (range 1 to 78 months). The mean age was 41.4 ± 13.8 years (range 21 to 59 years). At baseline, corrected distance visual acuity (CDVA) was 0.03 ± 0.08 logMAR. At the last follow-up, CDVA improved to 0.00 ± 0.03 logMAR (p = 0.029). Three of 20 eyes showed an improvement of 5 letters, while no loss of visual acuity was recorded during the follow-up time. Baseline CAS was 10.65 ± 12.69, and CAS at the last follow-up was 5.15 ± 5.49 (p = 0.068). Except for one patient, all were initially treated with intravenous (i. v.) steroids and subsequent oral tapering. Depending on the treatment response, cyclophosphamide (n = 4), i. v. immunoglobulins (IVIGs) (n = 4), anti-CD20 antibodies (n = 3), or plasmapheresis (n = 1) were applied. All patients under treatment for more than 1 month (n = 9) showed improvement in CAS and CDVA. CONCLUSION: Susac syndrome is a rare autoimmune vascular endotheliopathy. Treatment of Susac syndrome appears to result in improving CAS and CDVA. The majority of patients, in addition to the systemic steroids, required systemic immunosuppressive agents. Interdisciplinary communication is crucial to reduce the time to diagnosis and initiation of therapy in patients with Susac syndrome.

Imaging Assessment of Peripapillary Vessel Diameters in Postmortem Eyes.

PURPOSE: Proof of concept of ex vivo retinal vessel diameter measurements in human postmortem eyes. METHODS: En face near-infrared (IR) images and optical coherence tomography (OCT) of the optic nerve head (ONH) were captured ex vivo with a Heidelberg Engineering Spectralis (Spectralis, version 7.0.4, Image Capture Module, version 1.2.4, Heidelberg Heidelberg, Germany) device, using a custom-made eye chamber holding and positioning the eyes during the image process. Thirty-two formaldehyde-fixated eyes of 16 patients were imaged. In the IR images, two independent graders measured retinal vessel diameters at the intersection of a drawn circle centered on the ONH with diameters of 2.0 mm and 3.4 mm, respectively. The anatomically corresponding measurements between both graders were statistically analyzed using a Wilcoxon signed-rank test. RESULTS: A total of 246 matched measurements of both graders were analyzed across all 32 imaged eyes. Statistically significant differences between the graders were found for arterioles at 2 mm from the ONH. The other measurements did not show statistically significant intergrader differences. The mean values for arteriole diameters were 72.2 µm at 2.0 mm and 61.5 µm at 3.4 mm for grader 1, and 66.4 µm at 2.0 mm and 63.2 µm at 3.4 mm for grader 2. The mean diameter for venules were 75.5 µm at 2.0 mm and 79.3 µm at 3.4 mm for grader 1, and 67.4 µm at 2 mm and 79.1 µm at 3.4 mm for grader 2. CONCLUSION: To the best of our knowledge, this is the first study to present IR image-based retinal vessel diameters in ex vivo postmortem eyes. Retinal IR/OCT imaging is possible, and measurements are reproducible in formaldehyde-fixated human eyes. Fixation artefacts result in lower image quality, and this can impose challenges in correctly detecting, classifying, and measuring retinal vessels.

Severe Complications after Corneal Collagen Cross-Linking (CXL).

PURPOSE: To present a case series of rare and severe complications after corneal collagen cross-linking (CXL) of keratoconus patients. METHODS: Single-center descriptive case series covering the period of 2012 to 2022 at the Department of Ophthalmology at the University Hospital, Zurich, Switzerland. RESULTS: We present four eyes of four patients that showed severe unusual complications within the first month after CXL. Three patients had been treated with the classical epithelium-off "Dresden" protocol. One patient had been treated with the accelerated epithelium-off protocol. One patient presented with extensive corneal edema due to rubbing the eye after treatment. Two patients showed a bacterial infectious keratitis: one due to Streptococcus pneumoniae and the other due to Staphylococcus hominis, Micrococcus luteus, and Streptococcus epidermidis. The latter of the two patients exhibited extensive infectious crystalline keratopathy. The fourth patient showed a severe ulcerative lesion where no infectious cause could be found. Therefore, an autoimmune keratolytic process had to be suspected. Apart from the corneal edema, which resolved ad integrum, the other complications resulted in permanent corneal scarring and thinning. One patient needed an emergency amniotic transplant. CONCLUSION: Severe complications after CXL remain rare. Most common causes are complications that are not directly associated with the treatment as such. Those indirect complications occur after the treatment during the healing course of the epithelium. Associations with bandage contact lenses, topical steroids, atopic disease, and inappropriate patient behavior are often suspected. Correctly performed corneal scrapings with repeated microbiological analysis and a detailed patient history are essential for establishing the correct diagnosis, especially in complicated cases that do not respond to a standard therapeutic regimen. This case series supports the efforts that are currently taken to improve the CXL technique in a way that postoperative complications are further reduced. A more efficient epithelium-on technique might be a step in that direction.

Analysis of Blood Flow in the Macula and Optic Nerve Head in Healthy Young Volunteers Using Laser Speckle Flowgraphy.

PURPOSE: To assess optic nerve head (ONH) and macular blood flow in young healthy volunteers using laser speckle flowgraphy (LSFG). METHODS: This is a prospective single-center study conducted at the Department of Ophthalmology, University Hospital Zurich from May to November 2021. Young, healthy men aged ≥ 18 years without ocular or systemic diseases were included. A corrected visual acuity (VA) of 0.0 logMAR or better in both eyes and an intraocular pressure (IOP) of 21 mmHg or lower were required for inclusion. Subjects exceeding a spherical equivalent (SE) of ± 6 diopters (dpt) were excluded. Blood flow in the macula and the ONH was recorded using the Nidek LSFG RetFlow device (Nidek Company, Ltd., Hirioshi-cho, Japan). Laser power was set to 0.5 Millivolts (mV). Mean blur rate (MBR) was recorded as a parameter for blood flow. MBR is a calculated parameter that represents relative blood flow velocity correlated with the real anatomical blood flow rate. Colored heat maps of the recorded retinal area were generated automatically by the RetFlow device. RESULTS: Final analyses included 83 eyes of 43 male volunteers. Mean age was 21.9 years (SD ± 1.5, range: 20 to 29). Mean corrected VA was - 0.1 logMAR (SD ± 0.05, range: - 0.2 to 0.0), mean IOP was 15.4 mmHg (SD ± 2.5, range: 8.5 to 18.5), and mean SE was - 0.3 dpt (SD ± 1.2, range: - 5.0 to 1.2). Mean ONH MBR was 37.44 (SD ± 7.9, range: 22.5 to 53.5) and mean macular MBR was 27.8 (SD ± 9.7, range: 6.4 to 57.7). Pearson's Test showed a strong correlation between macular and papillary blood flow (p < 0.05, coefficient: 0.647). CONCLUSION: This study provides both ONH and macular blood flow data in a healthy young male population, showing a strong correlation between ONH and macular blood flow in the examined eyes. Further investigations are required to assess the validity of MBR as a parameter for the combined evaluation of retinal blood flow at the macula and ONH in healthy volunteers and patients with various diseases.

Natural Course of Solar and Laser-Associated Retinal and Macular Injuries at a Primary Care Hospital in Switzerland.

BACKGROUND: Solar and laser-associated retinopathies are rare occurrences. The two retinopathies are both photo-induced but differ in the involved intensity and duration of exposure. The purpose of this study was to evaluate the clinical features and natural course of these two entities, with a focus on the changes in the outer retina over time. PATIENTS AND METHODS: This retrospective analysis assessed patients with solar or laser maculopathy seen at the Department of Ophthalmology of the University Hospital Zurich in Switzerland over the last 10 years. Visual acuity (VA; Snellen) and optical coherence tomography (OCT) findings were reviewed and analyzed at baseline and last follow-up visit. Areas of damaged outer retina, identified on en face OCT images as hyporeflective areas, were tagged and compared between visits. Descriptive analysis was performed by calculating mean values ± standard deviation (SD). Statistical evaluation was done using the Wilcoxon signed rank test. A p value < 0.05 was considered statistically significant. RESULTS: Five patients with solar retinopathy and six patients with laser-associated retinopathy were identified. In the solar retinopathy group, mean VA at baseline was 0.80 (SD ± 0.37) and improved to 0.90 (SD ± 0.36). This was not statistically significant (p = 0.066). In the laser-associated retinopathy group, mean VA at baseline was 0.89 (SD ± 0.18) and improved to 1.03 (SD ± 0.09), which was not statistically significant either (p = 0.063). At baseline, in OCT cross-sections, initial changes were observed in the interdigitation, myoid, and ellipsoid zone, as well as the outer nuclear layer and the Henle fiber layer. At follow-up, most cases presented an alteration in the residual ellipsoid zone, with the degree of the aforementioned alterations depending on the size of the initial defect. A decrease of the hyporeflective alterations measured in en face OCT scans was observed in both groups but was only statistically significant in the laser-associated retinopathy group (p = 0.018 versus p = 0.172). CONCLUSIONS: OCT can help to detect and monitor solar and laser-associated retinal injuries. Most injuries are minor, with good functional restitution. Minor changes in the ellipsoid zone often persist, even in cases with full visual recovery.

Corneal Endothelial Decompensation after Ocular Chemical Burn: Description of a New Finding.

BACKGROUND: Ocular chemical burn is an ophthalmological emergency. Therefore, chemical injuries should be promptly addressed in order to initiate the appropriate treatment as soon as possible and optimize the visual prognosis. We present a retrospective study of ten cases with ocular chemical burn including one with superglue and one with a liquid plaster material injury and describe their clinical course. HISTORY AND SIGNS: Ten adult patients (34 - 92 years, 8 males) presented with moderate to severe alkali or neutral chemical burns in our emergency clinics. They exhibited a variable degree of conjunctival injection, limbal ischemia, corneal erosion, and Descemet's folds. THERAPY AND OUTCOME: Patients were treated and complete corneal epithelial closure was achieved in all cases without significant signs of limbal stem cell insufficiency. Corneal endothelial insufficiency was observed in all cases. Nine patients had to be listed for corneal endothelial keratoplasty and one was treated with Descemet's stripping endothelial automated keratoplasty. CONCLUSIONS: Isolated corneal endothelial decompensation after chemical burns has not yet been described. The pathophysiological explanation of this observation remains, however, unknown. In view of this rare complication, it is important to follow patients after chemical ocular burn for possible development of endothelial decompensation.

Immune dysregulation in patients with PTEN hamartoma tumor syndrome: Analysis of FOXP3 regulatory T cells.

BACKGROUND: Patients with heterozygous germline mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) experience autoimmunity and lymphoid hyperplasia. OBJECTIVES: Because regulation of the phosphoinositide 3-kinase (PI3K) pathway is critical for maintaining regulatory T (Treg) cell functions, we investigate Treg cells in patients with heterozygous germline PTEN mutations (PTEN hamartoma tumor syndrome [PHTS]). METHODS: Patients with PHTS were assessed for immunologic conditions, lymphocyte subsets, forkhead box P3 (FOXP3)+ Treg cell levels, and phenotype. To determine the functional importance of phosphatases that control the PI3K pathway, we assessed Treg cell induction in vitro, mitochondrial depolarization, and recruitment of PTEN to the immunologic synapse. RESULTS: Autoimmunity and peripheral lymphoid hyperplasia were found in 43% of 79 patients with PHTS. Immune dysregulation in patients with PHTS included lymphopenia, CD4+ T-cell reduction, and changes in T- and B-cell subsets. Although total CD4+FOXP3+ Treg cell numbers are reduced, frequencies are maintained in the blood and intestine. Despite pathogenic PTEN mutations, the FOXP3+ T cells are phenotypically normal. We show that the phosphatase PH domain leucine-rich repeat protein phosphatase (PHLPP) downstream of PTEN is highly expressed in normal human Treg cells and provides complementary phosphatase activity. PHLPP is indispensable for the differentiation of induced Treg cells in vitro and Treg cell mitochondrial fitness. PTEN and PHLPP form a phosphatase network that is polarized at the immunologic synapse. CONCLUSION: Heterozygous loss of function of PTEN in human subjects has a significant effect on T- and B-cell immunity. Assembly of the PTEN-PHLPP phosphatase network allows coordinated phosphatase activities at the site of T-cell receptor activation, which is important for limiting PI3K hyperactivation in Treg cells despite PTEN haploinsufficiency.