Conjunctival melanoma with pronounced central corneal invasion: One-year relapse free follow-up.

Purpose: Conjunctival melanoma with large corneal involvement is a rarity. We here present a case of conjunctival melanoma with pronounced central corneal involvement. Observation: A 69-year-old fair white male presented with a visual axis impeding corneal nodular lesion with associated conjunctival melanosis. Tumor excision with intraoperative mitomycin c (0.02 %) application for 180 seconds and amniotic membrane transplantation for defect coverage was performed in retrobulbar anesthesia. Histopathological evaluation revealed the nodular lesion to be a conjunctival melanoma (pT1a) with associated conjunctival melanocytic intraepithelial lesion (C-MIL). Conclusion and importance: Most conjunctival melanomas with corneal affection reach a radial corneal involvement of 1 mm. The here reported case accounted for 4 mm, which is seldom and therefore an important report. Surgical excision followed by intraoperative and postoperative mitomycin c exposure was a successful primary treatment. Currently there are no signs of tumor relapse in any part of the eye or the organism 12 months after excision. However, the long-term follow-up needs to be awaited.

The Alteration of Intraocular Pressure and Ocular Pulse Amplitude by Retrobulbar Anaesthesia-A Search for Risk Factors for Serious Complications Due to Retrobulbar Anaesthesia.

Our goal was to assess the impact of retrobulbar anaesthesia on ocular pressure and perfusion development and to find out if there were systemic or biometric parameters of patients affecting them in order to understand the effect of retrobulbar anaesthesia better. Methods: Changes in intraocular pressure (IOP) and ocular pulse amplitude (OPA) using a dynamic contour tonometer (DCT) were noted before and after retrobulbar anaesthesia (RBA) in combination with five minutes of oculopression at 40 mmHg in 134 patients. Only results with a quality Q 1-3 were considered for further statistical analysis. Systemic and ophthalmic parameters were noted and their impact was tested using linear regression. Results: IOP decreased from 18.9 ± 7.2 mmHg to 15.4 ± 6.3 mmHg (n = 71, p = 0.001) after first RBA. The dosage of midazolam administered during premedication was found to increase IOP significantly after first RBA (B = 3.75; R2 = 0.38). Ocular pulse amplitude decreased significantly from 3.8 ± 1.7 mmHg to 3.0 ± 1.9 mmHg after first RBA (n = 72, p < 0.001). This change was found to be dependent on the presence of diabetes mellitus (n = 68, p = 0.048). Conclusions: IOP and OPA decrease after RBA and oculopression. Caution is needed with midazolam premedication due to potential IOP increase. Patients with diabetes and pre-existing retinal or optic nerve damage should consider alternative anaesthesia methods, such as eye drops or general anaesthesia, due to the observed decrease in OPA after RBA and oculopression.

Impact of Intra-Retinal Fluids on Changes in Retinal Ganglion Cell and Nerve Fiber Layers in Neovascular AMD under Anti-VEGF Therapy.

Purpose: To investigate the influence of intraretinal fluid (IRF) on change in retinal nerve fiber layer (RNFL) and retinal ganglion cell layer (RGCL) and thickness in patients with naive neovascular AMD under anti-VEGF treatment. Design: post hoc analysis. Methods: 97 eyes of 83 patients on continuous therapy with intravitreal anti-vascular endothelial growth factors (anti-VEGF) and a follow-up of 24 months were included. RGCL and RNFL thickness in the perifoveal (-O), parafoveal (PF), and nasal areas and number of injections (IVI) were recorded before the first IVI as well as 1 and 2 years after initiating treatment and compared longitudinally and between groups with and without IRF. Results: The group with IRF at baseline had a higher RNFL thickness at baseline and showed a significant reduction in RNFL-PF between baseline and first and second follow-ups (p < 0.001) but not between first and second follow-ups. The group without IRF showed no significant reduction in RNFL over time. The presence of IRF was not associated with a reduction in RNFL-O or RNFL-nasal. RGCL thickness decreased significantly in both groups with and without IRF after 2 years. Number of IVIs showed no significant correlation to RNFL or RGCL after stratification for the presence of IRF. Conclusions: The presence of IRF has a significant influence on RNFL thickness at baseline as well as on its changes over time during anti-VEGF therapy. The preoperative presence of IRF should be considered when comparing changes in RNFL thickness after IVI.

CYR61/CCN1: A novel mediator of redox response in corneal stromal cells of keratoconus.

Keratoconus (KC) is a progressive, multifactorial and ectatic corneal disorder that characterized by steepening thinning of the cornea. It was previously demonstrated that oxidative stress has a strong link with KC progression. However, the molecular mechanism underlying oxidative stress response in KC remains unclear. Hence, the present study analyzed the heterogeneity of response of corneal stromal cells (CSCs) to oxidative stress in order to further illustrate how oxidative shape the pathophysiology of KC. Single-cell transcriptomics analysis revealed that CSCs demonstrated significant higher oxidative stress score in the KC group compared to the Ctrl group. The expression of oxidative markers verified by experiments illustrated elevated oxidative stress levels and insufficient antioxidant levels in CSCs of KC. In further single-cell transcriptomics analysis, we identified CYR61 to distinguish different subgroups of CSCs responding to oxidative stress. The cornea stroma cells in KC could be differentiated into CYR61high cells and CYR61low cells. Of note, the CYR61high cells showed lower score in collagen production process and higher score in collagen catabolic process. Further experiments illustrated that CYR61 was elevated in KC and associated with collagen production.

Epidemiology and phenomenology of the Charles Bonnet syndrome in low-vision patients.

BACKGROUND: The occurrence of visual hallucinations in visually impaired people without mental impairment is known as Charles Bonnet Syndrome (CBS). To date, the prevalence of CBS has been reported with high variance. The present study aims at evaluating the prevalence of CBS among low-vision patients. METHODS: From March 2018 to February 2022, 194 patients with a visual acuity ≥ 0.5 logMAR approached the low vision section of the Eye Clinic Sulzbach. Of these, 50 patients were found eligible, agreed to participate in the study and were screened for CBS. The course of the disease, its phenomenology and characteristics, the circumstance of onset, the ability to manipulate and resolve the hallucinations, and the psychosocial aspects of CBS were investigated. RESULTS: 26% of patients with low vision suffered from CBS. Women did not suffer from CBS significantly more often than men. Often, insight into the unreality of the images is not achieved immediately. Patterns or so-called "simple" hallucinations occurred just as frequently as other types of images such as people, body parts or faces. The most frequent images were animals. Visual hallucinations, lasting only for seconds in most cases, occurred more frequently during the day and in bright surroundings. All patients experienced the hallucinations exclusively with their eyes open. The hallucinations generally did not move with the eyes. Many sufferers did neither communicate about their hallucinations nor consult any physician. CONCLUSIONS: CBS among low-vision patients is common. Its prevalence constitutes clinical relevance. Future management of CBS may benefit from encouraging patients to share their experiences and consult a physician.

Effect of defocus incorporated multiple segments (DIMS) spectacle lenses on myopia progression in children: a retrospective analysis in a German real-life clinical setting.

OBJECTIVES: This retrospective analysis evaluates the treatment success of "Defocus Incorporated Multiple Segments" (DIMS) spectacle lenses in a real-life clinical setting in Germany. MATERIALS AND METHODS: Axial length (AL) and objective refraction of 166 eyes treated with DIMS at baseline and 12-month follow-up were analyzed. Annual AL growth rate within the range of physiological growth rate was considered a successful treatment. Myopia progression of ≥ -0.5 D/yr accounted as treatment success. Differences in percentages of treatment success of subgroups depending on baseline AL and age against treatment success of the total population were investigated. RESULTS: Considering all eyes, treatment success regarding AL growth and myopia progression was achieved in 46% and 65%, respectively. Male eyes with moderate AL showed treatment success in a higher proportion (73%, p < 0.01; 89%, p < 0.01); eyes with high AL showed treatment success in a lower proportion (25%, p < 0.01; 51%, n.s.). Female eyes showed the same trend but without statistical significance (moderate AL: 49%; 68%; high AL: 40%; 62%). Younger children showed treatment success in a lower proportion (male: 11%, p < 0.01; 38%, p < 0.05; female: 25%, p < 0.01; 42%, p < 0.01). Older children showed treatment success in a higher proportion (male: 60%, p < 0.05; 78% p < 0.05; female: 53%, n.s.; 77% p < 0.05). CONCLUSIONS: Eyes with moderate baseline AL and of older children showed treatment success after 12 months of DIMS treatment. Eyes with a high baseline AL and of younger children showed treatment success in a smaller proportion, therefore combination treatment should be considered. In future studies, males and females should be assessed separately.

[Bacterial keratitis : Clinical aspects, pathogens and treatment]. / Bakterielle Keratitis : Klinische Aspekte, Erreger und Therapie.

Bacterial infections are by far the most frequent cause of infectious keratitis in high-income countries. The clinical appearance can vary widely depending on the type and species of bacteria, ranging from small superficial infiltrates to necrotizing forms. The numerous classes of available antibiotics render the treatment scope diverse and complex, especially before the pathogen has been specified and the sensitivity to antibiotics has been tested. New therapeutic approaches to reduce bacterial virulence are in development. This CME article focuses on the clinical, diagnostic and therapeutic approaches to recognize and treat bacterial keratitis.

Outcomes of manual arcuate keratotomy with compression sutures for high regular postkeratoplasty astigmatism.

PURPOSE: To report functional and refractive outcomes of manual arcuate keratotomy (AK) with compression sutures for high regular postkeratoplasty astigmatism.Setting: not specified (review). DESIGN: Retrospective analysis. METHODS: This study included 90 eyes with high regular postkeratoplasty astigmatism (>4 diopters, D) who received AK with compression sutures between 2010 and 2022. Functional and refractive outcomes were assessed by evaluating topographic indices and by performing vector astigmatism and Fourier analysis. RESULTS: At last follow-up (mean=13.7±16.6 months), BCDVA improved from 0.59±0.28 logMAR to 0.34±0.25 logMAR. Cylinder magnitude decreased from 9.91±2.88 D to 5.42±3.35 D. Surface Asymmetry Index, Irregular Astigmatism Index, Corneal Eccentricity Index were equal to preoperative values, whereas Surface Regularity Index approached normal values at last follow-up. Fourier analysis indicated a decrease in the regular astigmatic component, whereas non-regular components (asymmetry and higher-order irregularity) remained stable. In vector astigmatism analysis, Target Induced Astigmatism magnitude was 9.92±2.86 D and Surgically Induced Astigmatism magnitude was 10.16±4.86 D (Correction Index of 0.91±0.48) with a Difference Vector of 5.42±3.35 D at last follow-up. Correction of astigmatism magnitude was adequate in 40% of the eyes, under-corrected in 30% and over-corrected in 30%. Angle of Error was <|22.5°| in 88% resulting in a low risk of off-axis treatment. CONCLUSION: AK with compression sutures is a simple, relatively effective and safe surgical procedure for astigmatism reduction after keratoplasty. In case of regular astigmatism, the procedure does not increase corneal irregularities. The remaining refractive error might be further corrected by spectacles, contact lenses or toric IOL implantation (in-the-bag / add-on), thus reducing the need for repeat keratoplasty.

Impact of Donor, Host, and Surgical Parameters on High Endothelial Cell Density More Than 5 Years after Penetrating Keratoplasty.

OBJECTIVES: To investigate the correlation between postoperative endothelial cell loss (ECL) and donor, host, and surgical parameters, and to assess the clinical impact of maintaining a high endothelial cell density (ECD) of ≥ 1500 cells/mm2 5 years after penetrating keratoplasty (PKP). METHODS: This retrospective cohort study included 216 eyes with 5 years of follow-up, of which 94 had annual visits, and who underwent normal-risk elective PKP for noninfectious indications by one corneal microsurgeon (B. S.) between 2009 and 2016. RESULTS: Among the 216 eyes, ECL (39.1%) over 5 years postoperative exhibited weak positive correlations with storage solution time (p = 0.024) and postmortem time (p = 0.028), and moderately positively correlations with the preoperative ECD (p < 0.001). The 5-year postoperative ECL differed significantly between in domo-prepared (36.8%) and ex domo donor corneas (46.3%; p = 0.001). In the 94 eyes, no significant differences were found between the two groups for central pupil pachymetry (CCT) and BCVA (p > 0.074). However, CCT increased significantly between 1 and 4 years (p = 0.034) and 1 and 5 years postoperatively (p = 0.012), respectively. BCVA improved significantly at 1 year postoperatively and continued to improve until 2 years postoperatively (p < 0.001). CONCLUSION: The Lions corneal bank Saar-Lor-Lux achieved a significantly reduced ECL (36.8%) over 5 years compared to ex domo donor corneas (46.3%). A weak positive correlation was found between ECL with the storage solution time and the postmortem time, as well as a moderate positive correlation with the preoperative ECD. Although CCT increased significantly over 5 years, BCVA improved significantly from the first to the second postoperative year and remained stable thereafter.

A Novel Symptomatic Lecithin-Cholesterol Acyltransferase Gene Mutation With Corneal Amyloidosis.

PURPOSE: To present ocular clinical, histological, systemic, and genetic findings of a patient with familial lecithin-cholesterol acyltransferase (LCAT) deficiency caused by a novel genetic variant of the LCAT gene associated with secondary corneal amyloidosis. METHODS: Case report. RESULTS: A 74-year-old woman presented with decreased visual acuity (VA), sensitivity to light, and progressive whitening of both corneas for approximately 20 years. The patient had undergone penetrating keratoplasty (PKP) on the right eye 6 years ago. Ophthalmologic examination revealed decreased VA in both eyes (OD: 0.05, OS: 0.3), and even further reduced glare VA (OD: 0.05, OS: 0.1), diffuse whitish corneal opacity involving the total thickness of the corneal stroma without crystalline deposits, and a marked peripheral diffuse arcus. Systemic examination revealed severely reduced plasma high-density lipoprotein cholesterol levels, target cells in blood smear, and chronic normochromic anemia. Clinically, LCAT deficiency was the most likely diagnosis. Further genetic analysis confirmed the diagnosis. The patient is homozygous for the novel variant c.943T>C (p.Trp315Arg) in the LCAT gene. Histologic examination of the cornea removed during the first keratoplasty revealed amyloid deposits. The cornea removed at the second keratoplasty had small vacuoles in the anterior stroma, indicating recurrence of lipid deposition. CONCLUSIONS: LCAT deficiency is a rare genetic disorder that can cause corneal opacities because of lipid deposition in the cornea. Systemic manifestations may help in the differential diagnosis to other diseases associated with severe high-density lipoprotein cholesterol reduction. Genetic analysis is employed to confirm the diagnosis. Some mutations in the LCAT gene seem to be associated with secondary corneal amyloidosis. Further investigation of this association is warranted. A recurrence of corneal opacity after PKP seems to occur mainly in the anterior corneal stroma.

Expression of matrix metalloproteinases and their inhibitors in corneal stromal fibroblasts and keratocytes from healthy and keratoconus corneas.

PURPOSE: To examine the in-vitro expression of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in corneal stromal cells by distinguishing between fibroblasts and keratocytes of healthy and keratoconus (KC) corneas. METHODS: Stromal cells were isolated from healthy and KC corneas (n = 8). A normal-glucose, serum-containing cell culture medium (NGSC-medium) was used for cultivation of healthy human corneal fibroblasts (HCFs) and KC human corneal fibroblasts (KC-HCFs). In order to obtain a keratocyte phenotype, the initial cultivation with NGSC-medium was changed to a low-glucose, serum-free cell culture medium for healthy (Keratocytes) and KC cells (KC-Keratocytes). Gene and protein expression of MMP-1, -2, -3, -7, -9 and TIMP-1, -2, -3 were measured by quantitative PCR and Enzyme-Linked Immunosorbent Assay (ELISA) from the cell culture supernatant. RESULTS: KC-HCFs demonstrated a lower mRNA gene expression for MMP-2 compared to HCFs. In contrast to their respective fibroblast groups (either HCFs or KC-HCFs), Keratocytes showed a higher mRNA gene expression of TIMP-3, whereas TIMP-1 mRNA gene expression was lower in Keratocytes and KC-Keratocytes. Protein analysis of the cell culture supernatant revealed lower concentrations of MMP-1 in KC-HCFs compared to HCFs. Compared to Keratocytes, TIMP-1 concentrations was lower in the cell culture supernatant of KC-Keratocytes. In HCFs and KC-HCFs, protein levels of MMP-1 and TIMP-1 were higher and MMP-2 was lower compared to Keratocytes and KC-Keratocytes, respectively. CONCLUSION: This study indicates an imbalance in MMP and TIMP expression between healthy and diseased cells. Furthermore, differences in the expression of MMPs and TIMPs exist between corneal fibroblasts and keratocytes, which could influence the specific proteolytic metabolism in-vivo and contribute to the progression of KC.

[The latest IC3D classification of corneal dystrophies-Overview and changes of the 3rd edition]. / Die aktuelle IC3D-Klassifikation der Hornhautdystrophien ­ Übersicht und Änderungen der 3. Auflage.

The International Committee on Classification of Corneal Dystrophies (IC3D) was founded in 2005 to address difficulties arising from the outdated nomenclature for corneal dystrophies (CD) and to correct misconceptions in the literature. For each of the 22 CDs, a separate template was created to represent the current clinical, pathological and genetic knowledge of the disease. In addition, each template contains representative clinical photographs as well as light and electron microscopic images and, if available, confocal microscopic and coherence tomographic images of the respective CD. After the first edition was published in 2008, the revised version followed in 2015. The third edition of the IC3D was published as open access in February 2024. The latest edition is intended to serve as a reference work in everyday clinical practice and facilitate the diagnosis of CD, which might sometimes be difficult. This article provides an overview of the diagnostic and treatment principles of CD and presents the IC3D and its changes over time.

Subfoveal choroidal thickness increases after excimer laser-assisted penetrating keratoplasty but not after excimer laser-assisted deep anterior lamellar keratoplasty.

To evaluate the impact of excimer laser-assisted deep anterior lamellar keratoplasty (Exc-DALK) and excimer laser-assisted penetrating keratoplasty (Exc-PKP) on subfoveal choroidal thickness (SFCT) in eyes with advanced keratoconus. A retrospective comparative clinical study, which compares the outcomes of 24 eyes treated with Exc-DALK (G1) against matched group of 43 eyes treated with Exc-PKP (G2) at both 2 months (T1) and 2 years (T2) postoperatively. Main outcomes included best-corrected visual acuity (BCVA), central macular thickness (CMT), and SFCT. Preoperatively, there were no significant differences between both groups regarding BCVA, CMT or SFCT (p > 0.05). There were no significant differences between both groups regarding BCVA at both follow-ups (p > 0.05). There were no significant differences between both groups regarding CMT at both follow-ups (p > 0.05). SFCT was higher in G2 than G1 at both follow-ups (p < 0.01). Compared to preoperative SFCT, there were no significant changes in SFCT in G1 at both follow-ups (p > 0.05). In G2, SFCT increased significantly at T1 (p < 0.01) and did not differ significantly at T2 (p = 0.17). SFCT increased significantly after Exc-PKP but not after Exc-DALK, which might indicate that Exc-DALK affects the choroid less and thus could represent a less traumatic approach to ocular tissue than Exc-PKP.

Electroporation with Calcium or Bleomycin: First Application in an In Vivo Uveal Melanoma Patient-Derived Xenograft Model.

Uveal melanoma (UM) represents a rare tumor of the uveal tract and is associated with a poor prognosis due to the high risk of metastasis. Despite advances in the treatment of UM, the mortality rate remains high, dictating an urgent need for novel therapeutic strategies. The current study introduces the first in vivo analysis of the therapeutic potential of calcium electroporation (CaEP) compared with electrochemotherapy (ECT) with bleomycin in a patient-derived xenograft (PDX) model based on the chorioallantoic membrane (CAM) assay. The experiments were conducted as monotherapy with either 5 or 10 mM calcium chloride or 1 or 2.5 µg/mL bleomycin in combination with EP or EP alone. CaEP and ECT induced a similar reduction in proliferative activity, neovascularization, and melanocytic expansion. A dose-dependent effect of CaEP triggered a significant induction of necrosis, whereas ECT application of 1 µg/mL bleomycin resulted in a significantly increased apoptotic response compared with untreated tumor grafts. Our results outline the prospective use of CaEP and ECT with bleomycin as an adjuvant treatment of UM, facilitating adequate local tumor control and potentially an improvement in metastatic and overall survival rates.

Natural History of Visual Acuity and Microperimetry-Based Functional Outcome Measures of the Macula in Patients with Geographic Atrophy: A Retrospective Chart Review Study in Germany.

Background/Objectives: Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) leading to the progressive and irreversible loss of visual function. Characteristics of GA include atrophic lesions resulting from the loss of photoreceptors, retinal pigment epithelium, and choriocapillaris. During GA progression, atrophic lesions typically advance from the macular periphery to the center, affecting foveal light sensitivity and visual acuity. This study analyzed changes in light sensitivity and visual acuity during the natural course of GA progression using the topographic analysis of structural and functional changes based on Early Treatment Diabetic Retinopathy Study (ETDRS) charts, multimodal imaging, and microperimetry assessment. Methods: Medical chart data of GA patients between 2014 and 2022 from the Internationale Innovative Ophthalmochirurgie GbR (I.I.O.) research center (Düsseldorf, Germany) were retrospectively analyzed. All patient eyes fulfilling the phase 3 OAKS study inclusion criteria were included and followed up for 60 months. The imputation of missing measurements and dropouts was performed by linear mixed models. Results: A total of 20 GA eyes from 13 GA patients were included in the study. At the index, 53.8% of patients had bilateral GA, with 70.0% of the eyes showing multifocal GA and 30.0% subfoveal encroachment (SFE). A total of 35.0% of the eyes had 2-5, and 15.0% over 20, areas of atrophy. Over time, the GA lesion size increased from 6.4 mm2 to 11.8 mm2 (1.08 mm2/year). After an average observation time of 2.9 years, 78.6% of the initially unaffected study eyes developed SFE. The percentage of study eyes without visual impairment decreased from 55.0% to 30.0%, with mean normal-luminance best-corrected visual acuity (NL-BCVA) reducing from 63.7 to 55.7 ETDRS letters. The share of absolute scotoma points in microperimetry assessment increased from 15.7% to 43.5% while overall average macular sensitivity declined from 15.7 dB to 7.4 dB. Conclusions: The substantial deterioration of macular outcomes and visual function was comprehensively detected. The results were a documentation of structural and functional aspects of the natural progression of GA for a 60-month follow-up, providing a typical outline for AMD patients with GA.