Identification of the regulatory circuit governing corneal epithelial fate determination and disease.

The transparent corneal epithelium in the eye is maintained through the homeostasis regulated by limbal stem cells (LSCs), while the nontransparent epidermis relies on epidermal keratinocytes for renewal. Despite their cellular similarities, the precise cell fates of these two types of epithelial stem cells, which give rise to functionally distinct epithelia, remain unknown. We performed a multi-omics analysis of human LSCs from the cornea and keratinocytes from the epidermis and characterized their molecular signatures, highlighting their similarities and differences. Through gene regulatory network analyses, we identified shared and cell type-specific transcription factors (TFs) that define specific cell fates and established their regulatory hierarchy. Single-cell RNA-seq (scRNA-seq) analyses of the cornea and the epidermis confirmed these shared and cell type-specific TFs. Notably, the shared and LSC-specific TFs can cooperatively target genes associated with corneal opacity. Importantly, we discovered that FOSL2, a direct PAX6 target gene, is a novel candidate associated with corneal opacity, and it regulates genes implicated in corneal diseases. By characterizing molecular signatures, our study unveils the regulatory circuitry governing the LSC fate and its association with corneal opacity.

PCR testing for herpesviruses in aqueous humor samples from patients with and without clinical corneal endothelial graft rejection.

To compare prevalence of positive PCR tests for herpesviruses between patients with and without a history of clinical corneal endothelial allograft rejection (AGR). Retrospective cross-sectional study with two-group comparison. A total of 307 aqueous humor (AH) samples from 235 Patients and 244 eyes who underwent penetrating keratoplasty or Descemet membrane endothelial keratoplasty or had a diagnostic AH aspiration due to clinical AGR between 2019 and 2023 were tested for DNA of herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). PCR test results were compared between the two groups (with/without AGR). Another sub-analysis examined the results of patients without a history of herpetic keratitis. A total of 8% of eyes with clinical AGR (9/108) had a positive PCR result for one of the herpesviruses (HSV:3, CMV:3, EBV:2, VZV:1). All patients in the group without AGR had negative PCR results for all previous viruses (0/136). The difference was statistically significant (p < 0.001). The sub-analysis of eyes without a history of herpetic keratitis also revealed significantly more positive herpes PCR results (7/87) in eyes with AGR than in eyes without AGR (0/42, p = 0.005). Clinical AGR after keratoplasty shows a significant correlation to viral replication. Herpetic infection and AGR could occur simultaneously and act synergistically. Timely differentiation between active herpetic infection and/or AGR is pivotal for proper treatment and graft preservation.

Short-term outcomes of intravitreal faricimab for refractory neovascular age-related macular degeneration.

PURPOSE: To assess the short-term outcomes of intravitreal faricimab (IVF) for previously treated refractory neovascular age-related macular degeneration (nAMD) in a real-world setting. METHODS: A retrospective monocentric study including 44 eyes treated with an upload of 4 × monthly intravitreal injections (IVI) of faricimab 6 mg/0.05 mL and followed for 4 weeks after last IVI (16 W). Patients were switched to IVF after treatment with at least three other anti-vascular endothelial growth factors (anti-VEGF). Main outcome measures included best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT) and retinal fluid distribution. RESULTS: 44 eyes of 44 patients with previously treated refractory nAMD (63% males) were included. Mean age was 79 ± 7 years. The total number of previous anti-VEGF before switching to IVF was 32 ± 15 IVIs/eye. BCVA (logMAR) improved significantly from 0.65 ± 0.26 to 0.50 ± 0.23 at 16 W (p < 0.01). CMT (µm) decreased significantly from 422 ± 68 to 362 ± 47 at 16 W (p < 0.01). SFCT did not change significantly at 16 W (p = 0.06). The number of eyes with subretinal fluid (SRF) decreased significantly from 29 (65%) to 13 (29%) at 16 W (p = 0.001). There were no significant changes regarding the distribution of intraretinal fluid or pigment epithelial detachment (p > 0.05). A complete fluid resolution was achieved in 8 eyes (18%). No adverse events were noticed. CONCLUSION: In the short term, IVF led to a significant decrease in CMT as well as a significant improvement of BCVA and thus appears to be an effective treatment option for previously treated refractory nAMD without relevant adverse effects.

Long-term choroidal thickness changes based on the subtype of macular neovascularization in neovascular age-related macular degeneration (5-year follow-up).

PURPOSE: To evaluate the long-term choroidal thickness changes in combination with other morphological and functional outcomes during anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (nAMD) based on the subtype of macular neovascularization (MNV): MNV-1 (within the subretinal pigment epithelium space) and MNV-2 (within the subretinal space). METHODS: This retrospective study included 58 eyes from 53 patients with naïve nAMD who received anti-VEGF therapy over a 60-month period. All eyes were treated initially with intravitreal bevacizumab following Pro re nata regimen. Main outcome measures included the following: subfoveal choroidal thickness (SFCT), best corrected visual acuity (BCVA), central macular thickness (CMT), development of subfoveal geographic atrophy (GA), and the number of injections. RESULTS: Thirty-four eyes had MNV-1 (group 1) and 24 eyes had MNV-2 (group 2). SFCT in group 1 vs group 2 was (210 ± 45 µm vs 191 ± 52 µm, p = 0.01) before treatment and (170 ± 47 µm vs 179 ± 48 µm, p = 0.24) after 60 months. BCVA (log MAR) in group 1 vs group 2 was (0.57 ± 0.18 vs 0.53 ± 0.22, p = 0.47) before treatment and (0.59 ± 0.23 vs 0.69 ± 0.16, p = 0.04) after 60 months. CMT in group 1 vs group 2 was (398 ± 154 µm vs 382 ± 103 µm, p = 0.86) before treatment and (297 ± 68 µm vs 283 ± 67 µm, p = 0.14) after 60 months. The number of injections per eye over a period of 60 months was significantly higher in group 1 (34.9 ± 11 vs 29.0 ± 14, p = 0.04). The proportion of eyes with subfoveal GA after 60 months was significantly higher in group 2 (13 eyes, 54%) than in group 1 (9 eyes, 25%) (p = 0.03). CONCLUSION: Over the full 60 months of anti-VEGF treatment, eyes with MNV-1 showed a greater reduction in choroidal thickness, better visual acuity, and less development of subfoveal geographic atrophy compared with eyes with MNV-2. The significantly thicker choroid in eyes with MNV type 1 at baseline seems to have a positive impact on long-term outcomes.

Surgical management of complicated Descemet's membrane detachment in corneas without prior endothelial keratoplasty.

PURPOSE: To provide insights into morphologic and functional features of eyes with complicated Descemet's membrane detachment (DMD) and report clinical outcomes after surgical intervention. METHODS: Retrospective study of 18 eyes with complicated DMD between 2010 and 2022. Complicated DMD was defined if any of the following criteria applied: prior penetrating keratoplasty (PKP), corneal thinning, total DMD or persistent DMD after Air/Gas-Descemetopexy. Causes, surgical management, and clinical outcomes were analyzed. Scheimpflug tomography, anterior segment optical coherence tomography (AS-OCT) and histologic examination were performed to characterize corneas with DMD. RESULTS: Fourteen eyes with prior PKP developed spontaneous DMD after 24.2 ± 12.9 years (range = 18 months - 47 years, median = 25.7 years). Complicated DMD without prior PKP was associated in three eyes after cataract surgery and in one eye after infectious keratitis. In cases with previous PKP, AS-OCT demonstrated rupture of Descemet's membrane (DM) in five eyes and spontaneous reattachment was found in four eyes within 8 weeks of initial diagnosis, with no rupture of DM in any of the cases. There was no rupture of DM in corneas without previous PKP. After prior keratoplasty, definitive surgical treatment was repeat PKP in 13 eyes and Air/Gas-Descemetopexy in one eye. In corneas without prior keratoplasty, three eyes underwent PKP and one eye Air/Gas-Descemetopexy. Histological examination of two corneal explants revealed a severely thinned graft-host junction and a disrupted DM close to the graft-host junction. Visual acuity improved from 1.80 ± 0.58 logMAR to 0.75 ± 0.69 logMAR after prior PKP and from 1.45 ± 0.65 logMAR to 0.85 ± 1.13 logMAR without prior PKP. The postoperative course was uneventful in 16 of 18 eyes. CONCLUSION: PKP is an effective treatment option for complicated DMD, especially in ectatic corneas, whereas Air/Gas-Descemetopexy or Descemet Membrane Endothelial Keratoplasty do not address the primary issue of the curvature anomaly.

Descemet Membrane Endothelial Keratoplasty after failed penetrating keratoplasty- case series and review of the literature.

BACKGROUND: This study aims to evaluate visual outcome, central corneal thickness, and re-bubbling rate in a cohort with undersized sequential Descemet Membrane Endothelial Keratoplasty (DMEK) due to endothelial graft decompensation following primary penetrating keratoplasty (PK). METHODS: All patients who received a sequential DMEK (n = 16) or triple DMEK (n = 2) after failed primary PK between November 2020 and June 2022 were retrospectively evaluated. Analyzed parameters were corrected distance visual acuity (CDVA), central corneal thickness (CCT), re-bubbling rate and graft survival. RESULTS: 18 eyes of 18 patients were included. All patients underwent a DMEK with undersized graft after failed PK(s). Mean time between the last PK and DMEK was 102 ± 82 weeks. Mean follow-up time was 8.9 ± 4.6 months. CDVA increased significantly from 1.12 ± 0.60 logMAR preoperatively to 0.64 ± 0.49 logMAR 6 weeks postoperatively (p = 0.013). Mean CCT decreased significantly from 807 ± 224 µm before to 573 ± 151 µm 6 weeks after DMEK (p = 0.003). Re-bubbling was necessary in eight eyes (44.4%) after a median time of 7 days. The 12-month Kaplan Meier survival was 66.7%. CONCLUSION: In case of endothelial graft decompensation without stromal scars after primary PK, a DMEK can be performed for selected patients who had satisfying CDVA before the endothelial decompensation. Prior to DMEK indication, an AS-OCT should routinely be performed to circularly search for posterior steps at the PK graft margin, as well as shortly after DMEK to exclude a detachment of the endothelial graft. All patients should be informed about a higher re-bubbling rate in comparison to primary DMEK.

Calcium Electroporation versus Electrochemotherapy with Bleomycin in an In Vivo CAM-Based Uveal Melanoma Xenograft Model.

Despite recent advancements in the diagnosis and treatment of uveal melanoma (UM), its metastatic rate remains high and is accompanied by a highly dismal prognosis, constituting an unmet need for the development of novel adjuvant therapeutic strategies. We established an in vivo chick chorioallantoic membrane (CAM)-based UM xenograft model from UPMD2 and UPMM3 cell lines to examine its feasibility for the improvement of selection of drug candidates. The efficacy of calcium electroporation (CaEP) with 5 or 10 mM calcium chloride (Ca) and electrochemotherapy (ECT) with 1 or 2.5 µg/mL bleomycin in comparison to monotherapy with the tested drug or electroporation (EP) alone was investigated on the generated UM tumors. CaEP and ECT showed a similar reduction of proliferation and melanocytic expansion with a dose-dependent effect for bleomycin, whereas CaEP induced a significant increase of the apoptosis and a reduction of vascularization with varying sensitivity for the two xenograft types. Our in vivo results suggest that CaEP and ECT may facilitate the adequate local tumor control and contribute to the preservation of the bulbus, potentially opening new horizons in the adjuvant treatment of advanced UM.

[Comparison of the Effect of Autologous Serum on Therapy Resistant Corneal Erosions and Ulcers on the Corneal Graft vs. the Patient's Own Cornea]. / Die Wirkung von autologen Serumaugentropfen bei therapieresistenten Erosiones und Ulcera der Kornea bei eigenem im Vergleich zu transplantiertem Gewebe.

PURPOSE: The aim of this study is to compare the healing of corneal epithelial defects or ulcers on the corneal graft in comparison with the patient's own cornea after treatment with 100%, undiluted autologous serum eye drops. METHODS: In a retrospective study over 7 years, we analysed 263 treatments with autologous serum eye drops of persistent corneal epithelial defects (erosions [88%] vs. ulcers [12%]). We compared the epithelial healing tendency of patients with defects on their own cornea (51.9%) vs. patients who had previously undergone penetrating keratoplasty (48.1%). Complete epithelial healing during the 28 days of treatment was considered as therapeutic success. In addition, the recurrence rate of the epithelial defects after finishing the therapy was analysed. RESULTS: 88.2% of the epithelial defects healed during 28 days of therapy. The recurrence rate during follow-up was 5.1%. There was no significant difference with respect to success rate between corneal defects on the patient's own cornea (87.8%) and on the graft (88.6%; p = 0.137). There was a significantly lower success rate for corneal ulcers (74.2%) than for erosions (90.3%; p < 0.001). The recurrence rate of erosions was 4.4%, vs. 4.3% in ulcers during follow-up. CONCLUSION: The results of our study suggest that autologous serum eye drops are a non-invasive and safe alternative treatment for persistent corneal epithelial defects - with no significant difference in patients with a defect on their own cornea vs. defects on the corneal graft. The success rate, but not the recurrence rate, is significantly worse in ulcers than in erosions.

Different Course of Immune Reactions and Endothelial Cell Loss after Penetrating Low-Risk Keratoplasty and Descemet Membrane Endothelial Keratoplasty for Fuchs Endothelial Dystrophy. / Unterschiedlicher Verlauf von Immunreaktionen und Endothelzellverlust nach perforierender Low-Risk-Keratoplastik und Descemet Membrane Endothelial Keratoplasty bei Fuchs-Endotheldystrophie.

BACKGROUND: The aim of this study was to compare the incidence of immune reactions and endothelial cell loss after penetrating keratoplasty (PKP) vs. Descemet membrane endothelial keratoplasty (DMEK) in patients with Fuchs endothelial dystrophy (FED). PATIENTS AND METHODS: In the present retrospective study, a total of 962 surgeries (225 excimer laser PKP and 727 DMEK) of 700 patients performed between 28.06.2007 and 27.08.2020 in the Department of Ophthalmology at Saarland University Medical Center UKS were statistically evaluated. On the one hand, the prevalence and the temporal course of the immune reactions that occurred were analysed using the Kaplan-Meier method, as well as the effect of the immune reactions on the endothelial cells and corneal thickness. Secondly, endothelial cell density, pleomorphism, and polymegethism of the endothelial cells were evaluated for the time points U1 = preoperative, U2 = 6 weeks postoperative, U3 = 6 to 9 months postoperative, U4 = 1 to 2 years postoperative, and U5 = 5 years postoperative. In addition, statistical tests were carried out for differences between the two types of surgery and in the longitudinal course. RESULTS: A total of 54 immune reactions occurred during the observed period, whereby the probability of such a reaction was significantly greater in the PKP group with 8.9% than in the DMEK group with 4.5% (p = 0.011). The comparison of the two Kaplan-Meier curves also showed a significant difference between the two surgical techniques in the log-rank test (p = 0.012). The endothelial cell loss due to the immune reaction was only significant in PKP (p = 0.003). For all surgical procedures, endothelial cell density decreased significantly with time in both surgical techniques (p < 0.0001 in each case), but more strongly with DMEK than with PKP (p < 0.0001). Furthermore, this cell density was significantly higher with PKP than with DMEK for the whole observation time (p < 0.0001). Polymegethism decreased significantly in the DMEK group (p < 0.0001). Pleomorphism was significantly higher, on average, in DMEK than in PKP (p < 0.0001). CONCLUSION: The prognosis of DMEK in patients with FED seems to be more favourable after immune reactions than that of PKP, as not only were immune reactions less frequent, but they were also milder. However, endothelial cell density was significantly higher in the PKP group during the entire follow-up.

Impact of Pachychoroid and DRIL on the Treatment of Diabetic Macular Oedema with Intravitreal Bevacizumab.

PURPOSE: To evaluate the long-term outcome of intravitreal bevacizumab in eyes with diabetic macular oedema (DME) following a PRN (pro re nata) regimen. Additionally, we investigated the effect of the presence of disorganisation of the retinal inner layers (DRILs) and pachychoroid (PC) at baseline on clinical outcome. METHODS: This retrospective study included 112 naïve eyes with DME that were followed up for 2 years. All eyes were treated with six initial bevacizumab injections at monthly intervals and then received treatment according to a PRN regimen. In case of poor response to bevacizumab, therapy was switched to other agents. Main outcome measures included: best-corrected visual acuity (BCVA), central macular thickness (CMT), and number of intravitreal injections (IVI s). In addition, we examined the effect of the presence of DRILs and PC at baseline on clinical outcome. RESULTS: BVCA improved significantly and CMT decreased significantly during the first 2 years of treatment. The number of IVI s per eye was 11.1 ± 4.8 at the end of the second year. Treatment had to be switched to other agents in 47 eyes (42%). The timing of switching was 12.4 ± 6.1 months after a mean of 9.2 ± 3.3 IVI s. Patients with DRILs at baseline (29.5%) had significantly worse BCVA at all time points before and after treatment, although CMT was significantly lower before treatment and comparable to patients without DRILs during treatment. Patients with PC at baseline (35.7%) had no significant differences in BVCA and CMT at all time points compared with patients without PC. CONCLUSIONS: This study demonstrates statistically significant functional and anatomical improvement in patients with DME treated with intravitreal bevacizumab after 2 years. However, more than 40% of eyes required a switch in therapy. The presence of DRILs at baseline had a negative effect whereas the presence of PC at baseline had no effect on clinical outcome.

Descemet Membrane Endothelial Keratoplasty (DMEK) Anesthesia Analysis.

PURPOSE: Comparison of safety and clinical results of Descemet membrane endothelial keratoplasty (DMEK) in topical, peribulbar, or general anesthesia. METHODS: Retrospective, post hoc matched study of 346 patients who received DMEK surgery with different types of anesthesia (n = 54 topical, n = 137 peribulbar, n = 155 general anesthesia). Outcome criteria were intraoperative complications, endothelial cell count (ECC), central corneal thickness (CCT) and graft rejection rate, rebubbling rate, and visual acuity (VA). Mean follow-up time was 9.4 ± 2.8 months. RESULTS: The group with topical anesthesia showed intraoperative difficulties such as vitreous pressure (p = 0.01) and difficult graft unfolding (p = 0.4), possibly leading to a higher rebubbling rate (p = 0.03) and therefore graft failure (p = 0.39). However, rebubbling and graft failure occurred more often when the graft preparation was more difficult (p = 0.2, p = 0.13, respectively), which was independent of anesthesia. All three groups achieved comparable functional results regarding VA, ECC, and CCT after 6 months. CONCLUSION: DMEK under topical anesthesia is feasible and shows comparable final visual outcomes but should be limited to selected cooperative patients and performed by experienced surgeons due to the potential for increased intraoperative challenges.

A Cross-sectional Analysis of 556 Eyes Entering the Homburg Aniridia Centre.

PURPOSE: Congenital aniridia is a severe malformation of almost all eye segments. In addition, endocrinological, metabolic, and central nervous systems diseases may be present. In order to develop better treatment options for this rare disease, an aniridia center must be established. The purpose of this work is to summarize ophthalmic findings of aniridia subjects examined at the Department of Ophthalmology, Saarland University Medical Center in Homburg. METHODS: Our retrospective single-center study included patients who underwent a comprehensive ophthalmic examination through the head of the KiOLoN ("Kinderophthalmologie", Orthoptics, Low Vision and Neuroophthalmology) Unit of the department between June 2003 and January 2022. Data at the first examination time point have been included. RESULTS: Of 286 subjects, 556 eyes of (20.1 ± 20.1 years; 45.5% males) were included. There was nystagmus in 518 (93.7%) eyes, and strabismus in 327 (58.8%) eyes. There were 436 (78.4%) eyes with age-appropriate axial length, 104 (18.7%) eyes with microphthalmos, and 13 (2.3%) eyes with buphthalmos. There was iris malformation with atypical coloboma in 34 eyes (6.1%), more than 6 clock hours of iris remnants in 61 eyes (10.9%), less than 6 clock hours of iris remnants in 96 eyes (17.2%), and complete aniridia in 320 (57.5%) eyes. The patients were graded according to the following aniridia-associated keratopathy (AAK) stages: Stage 0 (96 eyes [17.2%], no keratopathy), Stage 1 (178 eyes [32.0%]), Stage 2 (107 eyes [19.2%]), Stage 3 (67 eyes [12.0%]), Stage 4 (62 eyes [11.1%]), Stage 5 (45 eyes [8.0%]). There was secondary glaucoma in 307 (55.5%), macular hypoplasia in 395 (71.4%), and congenital optic nerve head pathology in 223 (40.3%) eyes. The iris malformation type was significantly positively correlated with AAK stage, lens properties, presence of glaucoma, congenital macular, and optic nerve head properties (p < 0.001 for all), while complete aniridia showed the most complications. CONCLUSIONS: At the Homburg Aniridia Center, the most common ophthalmic signs in congenital aniridia were AAK, iris malformation, cataract, and macular hypoplasia. The iris malformation type may indicate future expression of AAK, cataract, and glaucoma development and it is correlated with a congenital optic nerve head and macular pathology. Our registry will support further detailed longitudinal analysis of ophthalmic and systemic diseases of aniridia subjects during long-term follow-up.

Vision-Related Quality of Life among Patients with Different Types of Age-Related Macular Degeneration.

BACKGROUND: This study aimed to assess the vision-related quality of life (VRQol) of patients with age-related macular degeneration (AMD) and to evaluate VRQol according to different types of AMD. METHODS: In this small-scale, single-center, prospective investigation, patients with AMD and subjects without any signs of macular disease were asked to complete the NEI-VFQ-39. A total of 159 subjects were included and grouped according to the type of AMD as follows: 40 patients with dry AMD in both eyes (DD), 40 patients with exudative AMD in one eye (DE), 41 patients with exudative AMD in both eyes (EE), and 38 subjects without any signs of macular disease, as a control group (CG). RESULTS: The average age of the participants was 76 ± 7 years, and 44% were male. Most participants were retired (22.4%), and 75% of patients were initially diagnosed by their ophthalmologist. All the AMD groups had significantly worse overall VRQol than the CG. For general vision, near vision, mental health, and role difficulties, all the AMD groups had significantly lower scores than the CG. For distance vision, color vision, peripheral vision, driving difficulties, dependency, and social functioning, only patients in the EE and DE groups had significantly worse scores than the CG. The type of retinal fluid in patients with exudative AMD had no effect on overall VRQol; however, we found that the presence of pigment epithelial detachment could be associated with more role difficulties, such as completing work or working long hours. CONCLUSION: All types of AMD had a negative effect on vision-related quality of life. This effect was significantly more pronounced in patients with exudative AMD in at least one eye. However, the type of retinal fluid in patients with exudative AMD had no influence on their overall vision-related quality of life.

Acute bilateral vision loss after endovascular treatment of an intracranial aneurysm.

Acute bilateral vision loss (ABVL) is a rare and challenging diagnostic issue that is most often caused by a neurological disorder. Since it can be the presenting symptom of potentially life-threatening diseases, priority should be given to excluding such diagnoses. Special caution is required if ABVL symptoms result after an intracranial intervention. This article reports on a diagnostic approach for a patient suffering from ABVL due to vitreous hemorrhage related to a subarachnoid hemorrhage (SAH) after endovascular intracranial aneurysm treatment. This case study highlights the importance of imaging interpretation and its consequences.

In situ donor keratometry in deceased patients as a novel screening technique for eye banking.

PURPOSE: To investigate the potential role of keratometry on whole globes in situ of deceased patients by assessing its repeatability and comparing it with sterile donor tomography after excision and preservation in organ culture. METHODS: A sequence of 5 measurements was taken from 40 eyes in situ of deceased patients < 24 h after death using the portable Retinomax K-plus 3 (Bon, Tokyo, Japan). Keratometry of whole globes in situ, from which sclerocorneal discs were taken for organ culture, was compared to those obtained after measuring these sclerocorneal disks through their cell culture flask in medium I after 5 ± 4 days using the anterior segment optical coherence tomograph Casia 2 (Tomey Corp., Nagoya, Japan), and to 964 different donor corneas in medium II. RESULTS: Cronbach's alpha of the in situ keratometry was 0.891 and 0.942 for the steepest and flattest corneal power (P). The steepest (44.5D) and flattest (41.1D) P as well as the astigmatism (3.4D) of in situ corneas remained unchanged after preserving sclerocorneal discs in medium I (respectively 44.7D [p = 0.09]; 41.4D [p = 0.17]; 3.3D [p = 0.09]). The comparison of the in situ values with the 964 measured different donor corneas in medium II showed significantly (p < 0.001) higher P at the steep (45.4D) and flat (43.9D) meridian and smaller astigmatism (1.4D) for sterile donor tomography. CONCLUSIONS: Measuring deceased patients' eyes in situ with the portable Retinomax K-plus 3 represents a feasible and reliably repeatable screening method in the eye bank. In comparison to donor tomography in medium I, it measures a similar power and astigmatism.

Incidence and treatment approach of intraocular pressure elevation after various types of local steroids for retinal diseases.

PURPOSE: For the treatment of macular edema, in addition to the use of antivascular endothelial growth factors, steroids are also used intravitreally and sub-Tenon. Side effects include among others cataract formation and elevation of intraocular pressure (IOP). The aim of this retrospective study was to elicit the IOP elevation after administration of various steroidal medication, the time of onset, and the efficacy of the administered IOP-lowering therapies. METHODS: We included 428 eyes with a postoperative (n = 136), diabetic (n = 148), uveitic macular edema (n = 61), and macular edema after retinal vein occlusion (n = 83). These patients were treated with one or more diverse steroidal agents once or multiple times. These drugs included: triamcinolone acetonide (TMC) as intravitreal injection (TMC IVI) or sub-Tenon (TMC ST), as well as dexamethasone (DXM) and fluocinolone acetonide (FA) intravitreally. An increase of IOP of ≥ 25 mmHg was designated as pathological. A steroid response in anamnesis, the time of onset of IOP rise from the first administration, and the therapy administered were documented. RESULTS: Of 428 eyes, 168 eyes (39.3%) had IOP elevation up to a mean of 29.7 (SD ± 5.6) mmHg, which occurred at a median of 5.5 months. Steroids most frequently leading to rise of IOP included DXM (39.1% of all eyes receiving that drug), TMC IVI (47.6%), TMC ST combined with DXM (51.5%), DXM with FA (56.8%), and TMC IVI with DXM (57.4%). A Kaplan-Meier analysis and the Log Rank test showed a significant difference (p < 0.001). IOP rise was treated as follows: 119 conservatively (70.8%), and 21 surgically (12.5%, cyclophotocoagulation 8.3%, filtering surgery 1.8%, in 4 the steroidal drug implant was removed 2.4%), and 28 eyes received no therapy (16.7%). Sufficient IOP regulation was achieved in 82 eyes (68.9%) with topical therapy. In 37 eyes (31.1%) with persistently elevated intraocular pressure, topical therapy had to be continued over the follow-up of 20 ± 7 months. CONCLUSIONS: IOP increases after any type of steroid application are not rare. Results of our study let us suspect that especially therapy with intravitreal dexamethasone, either as a monotherapy or in combination with another steroid, tends to increase IOP more than other steroids. Regular IOP checks are necessary after each steroid administration, with possible initiation of long-term conservative and/or surgical therapy if necessary.

Reliability analysis of successive Corvis ST® measurements in keratoconus 2 years after accelerated corneal crosslinking compared to untreated keratoconus corneas.

PURPOSE: To assess the reliability of successive Corvis ST® measurements (CST, Oculus, Wetzlar, Germany) in keratoconus (KC) ≥ 2 years after accelerated corneal crosslinking (9 mW/cm2, 10 min, 5.4 J/cm2) compared to untreated KC corneas. METHODS: Three successive CST measurements per eye were performed in ≥ 2 years after CXL (CXLG, n = 20 corneas of 16 patients) and a control group consisting of non-operated, ABC-stage-matched KC corneas according to Belin's ABCD KC grading (controls, n = 20 corneas, 20 patients). Main outcome measures included maximal keratometry (Kmax), the Belin/Ambrósio-Enhanced-Ectasia-Deviation-Index BAD-D; the biomechanical parameters A1 velocity, deformation amplitude (DA) ratio 2 mm, Ambrósio relational thickness to the horizontal profile (ARTh), integrated radius, stiffness parameter A1 (SP-A1), and the Corvis Biomechanical Factor (CBiF, the linearized term of the Corvis Biomechanical Index). Mean values, standard deviations, and Cronbach's alpha (CA) were calculated. RESULTS: Both groups were tomographically comparable (BAD: 11.5 ± 4.7|11.2 ± 3.6, p = 0.682, Kmax: 60.5 ± 7.2|60.7 ± 7.7, p = 0.868 for controls|CXLG, paired t-test). A1 velocity (mean ± SD: 0.176 ± 0.02|0.183 ± 0.02, p = 0.090, CA: 0.960|0.960), DA ratio 2 mm (6.04 ± 1.13|6.14 ± 1.03, p = 0.490, CA: 0.967|0.967), integrated radius (12.08 ± 2.5|12.42 ± 1.9, p = 0.450, CA: 0.976|0.976), and CBiF (4.62 ± 0.6|4.62 ± 0.4, p = 0.830, CA: 0.965|0.965) were also comparable (controls|CXLG). ARTh was significantly higher in controls (177.1 ± 59, CA: 0.993) than after CXL (155.21 ± 65, p = 0.0062, CA: 0.993) and SP-A1 was significantly higher after CXL (59.2 ± 13, CA: 0.912) than in controls (52.2 ± 16, p = 0.0018, CA: 0.912). CONCLUSION: ARTh and SP-A1 differed significantly between controls and CXLG. Biomechanical measurements were generally of excellent reliability in both groups. CXL seems to affect biomechanical measurements of human corneas over more than 2 years.

Baseline Characteristics of 1976 Patients With Ectatic Corneal Disorders at a Single Center From 2010 to 2021: A Cross-Sectional Study of the Homburg Keratoconus Center.

OBJECTIVES: The study objective was to analyze the baseline characteristics of keratoconus (KC) patients at the Homburg Keratoconus Center from 2010 to 2021. METHODS: This cross-sectional study included 3,674 eyes, with analysis of demographics, clinical findings, visual function, endothelial measurements, and topographic, tomographic, and corneal biomechanical data from the first visit. RESULTS: Mean patient age was 36.3±13.8 years. The mean uncorrected distance visual acuity in log of minimal angle of resolution was 0.60 (20/80, Snellen equivalent), and the corrected mean was 0.3 (20/40). Of 1976 patients, 48.9% reported eye rubbing. Mean values (ranges) were 49.4±6.3 (36.3-78.0) D for steep keratometry, 462.4±66.0 (48.0-659.0) µm for thinnest corneal thickness, 9.7±8.7 (-0.5 to 88.8) for Belin/Ambrósio enhanced ectasia total deviation, 0.8±0.4 (0.0-1.0) for the Corvis biomechanical index, 0.9±0.2 (0.0-1.0) for the tomographic biomechanical index, 0.1±0.5 (-0.9 to 2.0) for the KC match index, 8.3±1.8 (2.2-17.7) mm Hg for corneal hysteresis, 7.1±2.2 (0.0-17.0) mm Hg for corneal resistance factor, and 2,562.9±326.3 (1,011-3,937) cells/mm2 for endothelial cell density. The average ABCDE KC stage was A2B3C1D1E2. Distance-corrected visual acuity correlated strongly with topometric, tomographic, and biomechanical data ( P <0.001). CONCLUSIONS: This comprehensive description of baseline features of KC patients at a tertiary center provides a reference for further longitudinal and international multicentric studies.

Differential Diagnosis of Keratoconus Based on New Technologies.

Keratoconus (KC) must be distinguished from other corneal ectatic diseases and thinning disorders for stage-appropriate and suitable management of each condition. The most relevant corneal pathologies that may imitate the tomographic KC pattern are pellucid marginal degeneration (PMD), keratoglobus, posterior keratoconus, and Fuchs-Terrien marginal degeneration (FTMD). In moderate cases of KC, differentiation is typically possible using slit lamp examination and corneal tomography with evaluation of the location of the corneal thinning region. In early cases, however, differential diagnosis may be more challenging since the cornea may look relatively normal. In severe cases, the extended area of corneal thinning also complicates differentiation. Biomicroscopic findings cannot always give all the information needed to distinguish KC from related ectatic corneal conditions. The aim of this work is to discuss contemporary techniques and findings to assist physicians to identify the correct diagnosis. Corneal topography has been used in recent decades as the main tool for imaging in ectatic corneal diseases. Moreover, Scheimpflug cameras (corneal tomographers), which analyze both anterior and posterior corneal surfaces, curvatures, pachymetry, elevation data, higher order aberrations, Fourier analysis of keratometric data, and corneal density have become the most promising tools for diagnosis and follow-up of ectatic diseases. A noninvasive air pulse tonometer in conjunction with an ultrahigh-speed Scheimpflug camera complements tomographic findings by analyzing biomechanical corneal properties. Α confocal microscopy system, which is a novel clinical technique for the study of corneal cellular structure, could contribute effectively in the same direction. Moreover, anterior segment optical coherence tomography (AS-OCT) creates cross-sections, which can be generated into a three-dimensional structure to produce corneal epithelial thickness (ET) measurements. ET mapping is increasingly recognized as a sensitive tool for the diagnosis of ocular surface disorders. Combining information of all these systems could lead to a more effective identification and differential diagnosis of ectatic corneal disorders.

Recurrent Filamentous Fungal Keratitis Caused When the Primarily Selected Graft Diameter was Too Small.

PURPOSE: To establish the importance of using a sufficiently large corneal graft in primary penetrating keratoplasty in order to prevent recurrence of fungal keratitis. OBERSERVATIONS: A 58-year-old female patient underwent emergency penetrating keratoplasty (diameter 7.0 mm, double running suture) for therapy-resistant fungal keratitis (Fusarium solani) at an external eye clinic. Despite intensive antifungal therapy, new fungal infiltrates appeared in the host cornea after a few days. The patient was referred to our department for further treatment. On first presentation, circular infiltrates were seen around the corneal graft with anterior chamber involvement and therapy-resistant hypopyon. We performed an emergency penetrating repeat keratoplasty (diameter of 13.0 mm, 32 interrupted sutures) combined with anterior chamber lavage and intracameral and intrastromal drug injection. CONCLUSION AND IMPORTANCE: Fungal keratitis sometimes has a frustrating clinical course. Therefore, early diagnosis with effective therapy initiation is of the utmost importance. In cases of penetrating keratoplasty, optimal planning and timing (before anterior chamber involvement) should be provided. Sufficient safety distance must be ensured in the choice of graft diameter, fixation with multiple interrupted sutures, and anterior chamber lavage, as well as intracameral and intrastromal drug administration. Incomplete excision carries a risk of recurrence and endophthalmitis in the course. Close postoperative control is necessary to detect early recurrences.