Factors influencing the outcomes of trabeculectomy, conventional canaloplasty, and mitomycin C augmented canaloplasty.

PURPOSE: To compare the efficacy, safety, and factors influencing the outcomes of trabeculectomy (TE), conventional canaloplasty (cCP), and mitomycin C augmented canaloplasty (mCP) in glaucoma patients. METHODS: Intraocular pressure (IOP), the number of IOP-lowering eye drops, and surgery-related complications were evaluated at baseline and through 18 months postoperatively. Correlations between patients' demographic data, ophthalmic and non-ophthalmic conditions, outcomes and complications were evaluated. RESULTS: 171 patients were included. IOP and IOP-lowering eye drops were significantly (p < 0.001) reduced 18 months after TE, cCP, and mCP. At the 18-month follow-up, IOP and IOP-lowering eye drops were significantly lower following TE than cCP (p < 0.001, p = 0.010, respectively) and mCP (p = 0.010, p = 0.014). At the 18-month follow-up, complete success rates were significantly higher after TE compared to cCP and mCP for IOP ≤ 21, 18, and 16 mmHg (p < 0.001). Qualified success rates for IOP ≤ 16 mmHg were higher following TE than cCP and mCP (p = 0.023). In the TE group, clinical hypotony at any postoperative follow-up was positively correlated with previous intravitreal anti-vascular endothelial growth factor (VEGF)-therapy (p < 0.001), leukaemia (p = 0.002), and a spherical equivalent < -3 dioptres (p < 0.001). There were no significant correlations in the cCP and mCP groups. CONCLUSION: TE, cCP, and mCP led to a significant reduction in IOP and IOP-lowering eye drops during 18 months of follow-up. At 18 months of follow-up, IOP and IOP-lowering eye drops were significantly lower following TE compared to cCP and mCP. Anti-VEGF-therapy, cystostatic therapy in leukaemia, and a spherical equivalent < -3 dioptres were significantly correlated with postoperative hypotony, macular folds, and choroidal detachment in the TE group. KEY MESSAGES: What is known • Trabeculectomy (TE) is considered the gold standard in the surgical management of glaucoma. However, TE involves extensive postoperative management and might be associated with severe surgery-related complications. What is new • In this study, intraocular pressure (IOP) and IOP-lowering eye drops were significantly lower following TE compared to conventional canaloplasty (cCP) and mitomycin C augmented canaloplasty (mCP) at a follow-up of 18 months. • In patients undergoing TE, anti-VEGF-therapy, cystostatic therapy in leukaemia, and a spherical equivalent < -3 dioptres were significantly correlated with postoperative hypotony, macular folds, and choroidal detachment.

Evaluating the 1-year success and safety of ab interno canaloplasty in combination with cataract surgery in glaucoma patients.

PURPOSE: To evaluate the treatment success and safety of ab interno canaloplasty (AbiC) combined with cataract surgery in glaucoma patients. METHODS: The prospective case study included 43 eyes that received an AbiC combined with cataract surgery (age 73.3 ± 8.2 years). The 360° microcatheterization and viscodilatation of the Schlemm's canal was conducted using VISCO 360 (Sight Sciences, CA, USA). The observation period was 12 months with visits at 2 and 6 as well as 12 months, 7 eyes were lost to follow up. RESULTS: The preoperative IOP was 19.8 ± 4.9 mmHg and was reduced to 14.5 ± 2.8 mmHg 12 months after AbiC (p < 0.0001). The relative IOP reduction was 23.6 ± 23.1% after 12 months. Topical glaucoma medication was also reduced from 2.4 ± 1.1 drugs to 1.1 ± 1.4 (p < 0.001) after 12 months. The complete surgical success rate (defined as IOP < 18 mmHg without topical therapy) was 31.6% whereas the qualified surgical success was 89.5% (IOP < 18 mmHg, with local therapy) There were no relevant intra- or postoperative complications. CONCLUSION: AbiC in combination with cataract surgery is a safe and effective procedure to achieve a significant reduction of IOP and local glaucoma medication 12 months after surgery.

[Glaucoma drainage devices in patients following injector-assisted implantation of an artificial iris into the ciliary sulcus : Video article]. / Glaukom-Drainage-Implantate bei Patienten nach injektorgestützter Implantation einer künstlichen Iris in den Sulcus ciliaris : Videobeitrag.

OBJECTIVE OF SURGERY: The aim of this surgical technique is the implantation of a glaucoma drainage device (GDD) in eyes with aphakic glaucoma following injector-assisted implantation of an artificial iris into the ciliary sulcus. INDICATIONS: This atraumatic tube insertion technique can be performed during GDD implantation after implantation of an artificial iris into the ciliary sulcus. SURGICAL TECHNIQUE: Following injector-assisted implantation of an artificial iris into the ciliary sulcus of eyes, the iris can shift into the chamber angle. The GDD should be positioned in the quadrant in which the iridectomy is located. Otherwise, GDD implantation is not possible due to the resistance of the artificial iris. Alternatively, the artificial iris can be easily and non-traumatically rotated in the ciliary sulcus by flushing the anterior chamber with balanced salt solution (BSS) to move the iridectomy into the desired area and position the GDD tube in the anterior chamber. A surgical video, which is available online, shows the surgical technique in detail. FOLLOW-UP: After GDD, dexamethasone eye drops should be applied 8 times daily for 1 week tapering down by 1 drop per week thereafter. Antibiotic eye drops, e.g., ofloxacin eye drops, are prescribed 4 times daily for 1 week and might be discontinued thereafter. EVIDENCE: To date, this is the first description of a rotation of an artificial iris located in the ciliary sulcus by irrigation of the anterior chamber during GDD implantation.

Effects of graft detachment on the central corneal thickness after uncomplicated Descemet membrane endothelial keratoplasty.

PURPOSE: To determine if early central corneal thickness (CCT) and best-corrected visual acuity (BCVA) changes indicate graft detachment after uncomplicated Descemet membrane endothelial keratoplasty (DMEK). METHODS: In this analysis of our prospectively collected ADDA registry data ( https://drks.de/search/de/trial/DRKS00027180 ), 45 pseudophakic eyes underwent DMEK surgery at the Department of Ophthalmology, RWTH Aachen University. Anterior segment optical coherence tomography (AS-OCT), the presence of stromal ripples on the posterior corneal surface, and BCVA measurements were assessed prior to, 1 day, 1 week, 1 month, and 6 months after surgery. RESULTS: Eyes were categorized into three groups: no graft detachment (group 1) (20/45; 44.4%), < 1/3 graft detachment (group 2) (14/45; 31.1%), ≥ 1/3 graft detachment followed by rebubbling (group 3) (11/45; 24.4%). Eyes in group 3 had a greater CCT prior to (746.8 ± 95.8 µm vs. 665.0 ± 74.4 µm, P = 0.041), and 1 week (666.8 ± 119.5 µm vs. 556.5 ± 56.8 µm, P = 0.001) after DMEK compared to group 1. By 1 month, CCT in all groups aligned. Comparing prior to and 1 week after DMEK, none of the eyes in group 1 had an increase in CCT, while the CCT increased in 25.0% of eyes in group 2 and 22.2% in group 3. In group 1, 90.0% had a CCT of < 600 µm 1 week after DMEK, compared to only 50.0% in group 2 and 36.4% in group 3. In group 1, 90.0% (18/20) had an improved BCVA 1 week after DMEK, while in groups 2 and 3, 86.7% (12/14) and 18.2% (2/11) improved, respectively. One patient in group 3 showed posterior stromal ripples 1 day and 1 week after DMEK. CONCLUSION: If 1 week after uncomplicated DMEK CCT is < 600 µm and has decreased from before surgery, BCVA has improved, and there are no posterior stromal ripples, a graft detachment ≥ 1/3 and the need for rebubbling are very unlikely. In all other cases, meticulous slit-lamp and OCT inspection of the peripheral graft for detachments should be advised.

Clinical, Anatomical, and Densitometric Changes following Dresden vs. Accelerated Corneal Cross-Linking in Progressive Keratoconus.

BACKGROUND: To compare clinical, anatomical, and densitometric changes following Dresden (DCXL) vs. accelerated (ACXL) corneal UVA cross-linking (CXL; Avedro KXL, Geuder, Heidelberg, Germany) in progressive keratoconus (KC). METHODS AND MATERIAL: In this retrospective study, we analyzed 20 patients following DCXL (3 mW/cm², 30 min, 5.4 J/cm²) and 44 patients following ACXL (9 mW/cm², 10 min, 5.4 J/cm²) between January 2016 and February 2020. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), steepest keratometry (Kmax), keratoconus index (KI), thinnest pachymetry (Pthin), and corneal densitometry (CD) were measured before and 3, 6, 12, and 24 months after CXL. RESULTS: During the follow-up period, no changes in UCVA, BSCVA, Kmax, KI, or Pthin occurred. CCT significantly decreased 3 months after DCXL (p = 0.032) and ACXL (p = 0.006). At the 12- and 24-month follow-up, CCT remained decreased in the DCXL (p = 0.035, 0.036, respectively) but not in the ACXL group. At the 12-month follow-up, the reduction in CCT was significantly greater in DCXL compared to ACXL (p = 0.012). At the 3-, 6-, 12-, and 24-month follow-ups, we found a significant increase in the anterior stroma CD following DCXL (p = 0.019, 0.026, 0.049, 0.047, respectively) but not ACXL. The CD changes were localized in the central concentric zones (0.0 to 6.0 mm). No intra- or postoperative complications occurred. CONCLUSION: ACXL and DCXL effectively halted KC progression. ACXL proved to be a safe time-saving alternative to conventional DCXL. DCXL led to a reduction in CCT and an increment in the CD of the central anterior stroma during 24 months of follow-up.

Efficacy of citicoline as a supplement in glaucoma patients: A systematic review.

PURPOSE: Glaucoma is a leading cause of irreversible blindness worldwide. Retinal ganglion cells (RGC), the neurons that connect the eyes to the brain, specifically die in glaucoma, leading to blindness. Elevated intraocular pressure (IOP) is the only modifiable risk factor, however, many patients progress despite excellent IOP control. Thus, alternative treatment strategies to prevent glaucoma progression are an unmet need. Citicoline has demonstrated neuroprotective properties in central neurodegenerative diseases. However, conclusive evidence of the effect of citicoline on glaucoma progression is missing. This systematic review investigates first-time the therapeutic potential of citicoline in glaucoma patients. METHODS: The present study was conducted according to the PRISMA 2020 statement. PubMed, Web of Science, Google Scholar, and Embase were accessed in July 2023 to identify all clinical studies investigating the efficacy of citicoline on IOP, the mean deviation of the 24-2 visual field testing (MD 24-2), retinal nerve fibre layer (RNFL), and the pattern electroretinogram (PERG) P50-N95 amplitude in glaucoma patients. The risk of bias was assessed using the Review Manager 5.3 software (The Nordic Cochrane Collaboration, Copenhagen) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tool. RESULTS: Ten studies were eligible for this systematic review, including 424 patients. The mean length of the follow-up was 12.1 ± 11.6 months. The overall risk of bias was low to moderate. The mean age of the patients was 56.7 years. There were no significant differences in the IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude between patients receiving citicoline and the control group. There was no improvement from baseline to the last follow-up in IOP, MD 24-2, RNFL, or PERG P50-N95 amplitude. CONCLUSION: There is a lack of sufficient evidence to support that citicoline slows the progression of glaucoma.

Efficacy of allogenous fascia lata grafts in the management of lower eyelid retraction.

PURPOSE: To report on the use of allogenous fascia lata (FL) grafts in patients with lower eyelid retraction (LER). METHODS: In this retrospective study, a consecutive series of 27 patients (39 eyes) with LER who underwent lower eyelid elevation with FL was included. Examinations including measurement of the palpebral fissure vertical height (PFVH), the inferior scleral show distance, the margin reflex distance 2 (MRD 2), and the evaluation of conjunctival hyperemia were conducted at baseline and after a mean postoperative time of 25.9 ± 25.5 (5.0-81.0, median 13.0, last follow-up) months in all patients. RESULTS: At the last follow-up, a significant reduction of the PFVH (11.3 ± 1.7 versus 12.8 ± 2.1 at baseline, p < 0.001), the inferior scleral show distance (0.7 ± 1.0 mm versus 2.1 ± 1.1 at baseline, p < 0.001), and the MRD 2 (6.4 ± 0.9 versus 7.8 ± 1.3 at baseline, p < 0.001) occurred. The conjunctival hyperemia grading score (McMonnies) was significantly reduced (1.8 ± 0.7) at the last follow-up compared to baseline (2.6 ± 0.6, p < 0.001). No case of ectropion or entropion was observed at the last follow-up visit. CONCLUSION: In this case series, lower eyelid elevation with FL grafts as a spacer led to a significant reduction of the PFVH, MRD 2, inferior scleral show distance, and conjunctival hyperemia. No severe surgery-related complications occurred.

P32-A134†Cytoprotective effects of human platelet lysate during the xeno-free culture of human donor corneas.

PURPOSE: We evaluated the suitability of 2% human platelet lysate (2%HPL) to replace 2% fetal bovine serum containing medium (2%FBS) for the xeno-free organ culture of human donor corneas. METHODS: 32 human corneas unsuitable for transplantation from 16 human donors (age 69.3±15.7years) were collected 38.5±17.1 hours after death. They were first cultured in 2%FBS containing medium for 3 days (time point TP1), then evaluated by phase contrast microscopy (endothelial cell density (ECD) and cell morphology. Following an additional 25-days culture period (time point TP2) in either 2%FBS or 2%HPL medium the pairs were again compared by phase contrast microscopy (ECD and morphology), stroma and Descemet membrane/endothelium (DmE) were processed for next generation sequencing (NGS). RESULTS: ECD did not differ between the 2%HPL and 2%FBS group at TP1 (p=0.87). At TP2 the ECD was higher in the 2%HPL group (2179±288cells/mm2) compared to 2%FBS (2113±331cells/mm2; p=0.03), and endothelial cell loss was lower (ECL hPL=-0.7% vs. FBS=-3.8%; p=0.01). There were no significant differences in cell morphology, neither between TP1 and 2 nor between 2%HPL and 2%FBS. NGS showed the differential expression of 1644 genes in endothelial and 217 genes in stromal cells. 2%HPL led to the upregulation of cytoprotective, anti-inflammatory and anti-fibrotic genes (e.g. HMOX1, SERPINE1, ANGPTL4, LEFTY2, GADD45B, PLIN2, PTX3, GFRA1/2) and the downregulation of pro-inflammatory/apoptotic genes (e.g. CXCL14, SIK1B, PLK5, PPP2R3B, SLURP1, FABP5, MAL, GATA3). CONCLUSION: 2%HPL is a suitable xeno-free substitution for 2%FBS in human cornea organ culture, inducing less ECL and potentially beneficial alterations in gene expression.

P05-A152†Human platelet lysate for cornea organ culture.

PURPOSE: Comprehensible concerns have been raised regarding the safety of FBS-based culture media. In this talk we discuss the benefits of using human platelet lysate (HPL) for the xeno-free culture of human donor corneas, isolated corneal stromal keratocytes (CSK) and stromal fibroblasts (SF). METHODS: 32 human corneas unsuitable for transplantation from 16 human donors were cultured for 25-days in either 2%FBS or 2%HPL medium and compared by phase contrast microscopy (ECD and morphology), and next generation sequencing (NGS). Effects of 0.5%FBS, 5%FBS, 0.5%HPL, 2%HPL and 10%hPL on cultured human CSK and SF were evaluated. RESULTS: Differential cornea culture showed lower endothelial cell loss in the 2%HPL vs. 2%FBS group (ECL hPL=-0.7% vs. FBS=-3.8%; p=0.01). 2%HPL led to the upregulation of cytoprotective, anti-inflammatory and anti-fibrotic genes (e.g. HMOX1, SERPINE1, ANGPTL4, LEFTY2) and the downregulation of pro-inflammatory/apoptotic genes (e.g. CXCL14, SIK1B, PLK5, PPP2R3B). CSK/SF cell viability remained high in all groups (98-100%). Cell numbers and proliferation rates increased (p=0.024-0.001), CSK marker expression decreased with higher fractions of HPL and FBS (p<0.001). SMA1 increased with higher amounts of FBS (p=0.003) but decreased with incremental HPL substitution in both cell types (p=0.014). HPL contained more TGF-ß1 (100%hPL 1.861±0.231ng/ml vs. 100%FBS 0.015±0.010ng/ml, p<0.001). bFGF and HGF were only detectable in 100% hPL (bFGF 0.067±0.017ng/ml, HGF 1.074±0.050ng/ml). CONCLUSION: 2%HPL is a suitable xeno-free substitution for 2%FBS in human cornea organ culture, inducing less ECL and potentially beneficial alterations in gene expression. CSK and SF can be cultured with xeno-free hPL. To maintain CSK characteristics substitution must remain minimal (0.5% hPL/FBS). hPL contains the antifibrotic HGF und bFGF, suppressing myofibroblast conversion.

Chloroquine and Hydroxychloroquine in the Treatment of Dry Eye Disease.

The role of chloroquine (CQ) and hydroxychloroquine (HCQ) in the management of dry eye disease is still unclear. This systematic review and meta-analysis investigates the efficacy and feasibility of CQ and HCQ in patients with dry eye disease. In February 2023, PubMed, Embase, Google Scholar, and Web of Science were accessed. Data from 462 patients (mean age 54.4 ± 2.8 years) were collected. Compared to baseline, the tear breakup time (p < 0.0001) and Schirmer I test (p < 0.0001) were significantly increased, and the Ocular Surface Disease Index (OSDI, p < 0.0001) and corneal staining (p < 0.0001) were significantly decreased at the last follow-up in the CQ/HCQ group. At the last follow-up, the OSDI was significantly lower in the CQ/HCQ group compared to the control group (p < 0.0001). Corneal staining was significantly greater in the control group compared to the CQ/HCQ group (p < 0.0001). The Schirmer I test showed no significant difference between the groups (p = 0.2). Altogether, CQ and HCQ improved the symptoms and signs of dry eye disease.

Honey-Related Treatment Strategies in Dry Eye Disease.

This systematic review and meta-analysis investigated whether honey-related treatment strategies improve the signs and symptoms of patients with dry eye disease (DED). In March 2023, the following databases were accessed for clinical trials investigating the efficacy of honey-related treatment strategies in DED: PubMed, Web of Science, Google Scholar, and EMBASE. The following data were extracted at baseline and at the last follow-up: Ocular Surface Disease Index, tear breakup time, Schirmer I test, and corneal staining. Data from 323 patients were retrieved (53.3% female, mean age 40.6 ± 18.1 years). The mean follow-up was 7.0 ± 4.2 weeks. All the endpoints of interest significantly improved from baseline to the last follow-up: tear breakup time (p = 0.01), Ocular Surface Disease Index (p < 0.0001), Schirmer I test (p = 0.0001), and corneal staining (p < 0.0001). No difference was found in tear breakup time (p = 0.3), Ocular Surface Disease Index (p = 0.4), Schirmer I test (p = 0.3), and corneal staining (p = 0.3) between the honey-related treatment strategies and the control groups. According to our main results, honey-related treatment strategies are effective and feasible to improve symptoms and signs of DED.

Molecular and Cellular Mechanisms of Corneal Scarring and Advances in Therapy.

On the basis of WHO global blindness data, it may be stated that 23 million people globally suffer from unilateral corneal blindness, while 4 [...].

12-month outcomes of ab interno excisional goniotomy combined with cataract surgery in primary open-angle glaucoma and normal tension glaucoma.

PURPOSE: To evaluate the efficacy and safety of excisional goniotomy performed with the Kahook Dual Blade (KDB) combined with cataract surgery in patients with pimary open angle glaucoma (POAG) and Normal Tension Glaucoma (NTG) under topical therapy. Further sub-analysis was performed to compare between 90 and 120 degrees goniotomy. METHODS: This was a prospective case series of 69 eyes from 69 adults (age 78 ± 5.9 years; male = 27, female = 42). Indications for surgery included insufficient IOP control with topical medication, glaucomatous damage progression under topical therapy and reduction of medication burden. Complete success was defined as IOP lowering below 21 mmHg without the need for topical medication. For NTG patients, complete success was defined as IOP lowering below 17 mmHg without the need for topical medication. RESULTS: IOP was significantly lowered from 19.7 ± 4.7 to 15.1 ± 2.7 at 2 months, 15.8 ± 2.3 at 6 months and 16.1 ± 3.2 at 12 months (p < 0.05) for POAG and 15.1 ± 2.5 to 14.1 ± 2.4 at 2 months, 14.1 ± 3.1 at 6 months and 13.6 ± 1.8 at 12 months (p > 0.08) for NTG, respectively. Complete success was achieved in 64% of the patients. IOP lowering under 17 mmHg without the need for topical medication was achieved in 60% of the patients at 12 months. In NTG patients (14 eyes) IOP lowering under 17 mmHg without the need for topical medication was achieved in 71%. No significant difference was recorded in terms of IOP lowering at 12 months in-between 90° and 120° of treated trabecular meshwork (p > 0.7). No severe adverse reactions were recorded in this study. CONCLUSION: One-year results show that KDB combined with cataract surgery is an effective treatment option for glaucoma patients. IOP lowering was successfully achieved in NTG patients with complete success in 70% of the patients. In our study, no significant differences were recorded in-between 90° and 120° of treated trabecular meshwork.

[Ab interno trabeculotomy without/with cataract operation-An alternative treatment before or instead of trabeculectomy in patients with high intraocular pressure?] / Ab-interno-Trabekulotomie ohne/mit Kataraktoperation ­ Eine Therapiealternative vor bzw. anstatt Trabekulektomie bei Patienten mit hohen Augeninnendrücken?

BACKGROUND: Trabeculotomy with the Kahook knife is a new ab interno minimally invasive glaucoma surgery (MIGS) procedure. The MIGS are usually performed in early to intermediate glaucoma eyes. In this retrospective study we analyzed the intraocular pressure (IOP) and topical glaucoma eye drop therapy (Meds) reduction achieved by the Kahook trabeculotomy (TO) without (n = 19) or with (n = 18) combined cataract operation (Cat-TO) as initial treatment before or to avoid filtering surgery. MATERIAL AND METHODS: A total of 37 eyes of 37 patients were examined when IOP was > 21 mm Hg in at least 2 examinations despite the maximum tolerable Meds applied. Cat-TO was performed in 18 phakic eyes (primary open-angle glaucoma, POAG = 11, pseudoexfoliation glaucoma, PEX = 5, ocular hypertension, OHT = 2). In 19 pseudophakic eyes (POAG = 12, PEX = 6, OHT = 1) an isolated TO was executed. Complete success (no Meds) and relative success (irrespective of Meds) for IOP ≤ 21 mm Hg, ≤ 18 mm Hg, ≤ 16 mm Hg were evaluated 2, 6 and 12 months postoperatively. RESULTS: The IOP was significantly reduced from preoperatively to 2 months after Cat-TO as well as after TO (Cat-TO: 26.8 ± 5.9 mm Hg to 16.0 ± 2.9 mm Hg, p < 0.001; TO: IOD 28.2 ± 5.6 mm Hg to 16.3 ± 3.5 mm Hg, p < 0.001). Meds reduction after Cat-TO as well as after TO was not significant (Cat-TO: 2.1 ± 1.3 to 1.3 ± 1.3, p = 0.11; TO: Meds 2.7 ± 1.1 to 2.2 ± 1.3, p = 0.23); however, Meds reduction after 6 and 12 months was significantly greater in the Cat-TO group compared to the TO group (p = 0.02). The IOP and Meds did not change significantly from 2 to 6 months. After Cat-TO, qualified success after 12 months for IOP ≤ 18 mm Hg was 61% (11/18) and for IOP ≤ 16 mm Hg 28% (5/18). After TO, qualified success after 12 months for TO was 47% (9/19) for IOP ≤ 18 mm Hg and 26% (5/19) for IOP ≤ 16 mm Hg. The intervention was not sufficient for 7 patients after TO and 2 patients after Cat-TO (IOP two times > 21 mm Hg). CONCLUSION: The first year results show that TO as well as Cat-TO are effective minimally invasive interventions to delay or even avoid a filtrating operation. In case of Meds intolerance and target IOP ≤ 16 mm Hg Cat-TO is not sufficient.

Current Practice in the Treatment of Epithelial and Melanocytic Tumours with Interferon-α2b: A Survey of Tertiary Eye Centres in Germany.

PURPOSE: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany. METHODS: A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon-α2b eye drops and subconjunctival injections. RESULTS: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b were its high cost and the reimbursement thereof. CONCLUSION: Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon-α2b being the standard second-line option. Interferon-α2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon-α2b are likely to have a profound impact on patient care and their quality of life.

Cytoprotective Effects of Human Platelet Lysate during the Xeno-Free Culture of Human Donor Corneas.

We evaluated the suitability of 2% human platelet lysate medium (2%HPL) as a replacement for 2% fetal bovine serum medium (2%FBS) for the xeno-free organ culture of human donor corneas. A total of 32 corneas from 16 human donors were cultured in 2%FBS for 3 days (TP1), then evaluated using phase contrast microscopy (endothelial cell density (ECD) and cell morphology). Following an additional 25-day culture period (TP2) in either 2%FBS or 2%HPL, the pairs were again compared using microscopy; then stroma and Descemet membrane/endothelium (DmE) were processed for next generation sequencing (NGS). At TP2 the ECD was higher in the 2%HPL group (2179 ± 288 cells/mm2) compared to 2%FBS (2113 ± 331 cells/mm2; p = 0.03), and endothelial cell loss was lower (ECL HPL = -0.7% vs. FBS = -3.8%; p = 0.01). There were no significant differences in cell morphology between TP1 and 2, or between 2%HPL and 2%FBS. NGS showed the differential expression of 1644 genes in endothelial cells and 217 genes in stromal cells. It was found that 2%HPL led to the upregulation of cytoprotective, anti-inflammatory and anti-fibrotic genes (HMOX1, SERPINE1, ANGPTL4, LEFTY2, GADD45B, PLIN2, PTX3, GFRA1/2), and the downregulation of pro-inflammatory/apoptotic genes (e.g., CXCL14, SIK1B, PLK5, PPP2R3B, FABP5, MAL, GATA3). 2%HPL is a suitable xeno-free substitution for 2%FBS in human cornea organ culture, inducing less ECL and producing potentially beneficial alterations in gene expression.

Antifibrotic Effects of Caffeine, Curcumin and Pirfenidone in Primary Human Keratocytes.

We evaluated the small molecules (AFM) caffeine, curcumin and pirfenidone to find non-toxic concentrations reducing the transformation of activated human corneal stromal keratocytes (aCSK) to scar-inducing myofibroblasts (MYO-SF). CSK were isolated from 16 human corneas unsuitable for transplantation and expanded for three passages in control medium (0.5% FBS). Then, aCSK were exposed to concentrations of caffeine of 0−500 µM, curcumin of 0−200 µM, pirfenidone of 0−2.2 nM and the profibrotic cytokine TGF-ß1 (10 ng/mL) for 48 h. Alterations in viability and gene expression were evaluated by cell viability staining (FDA/PI), real-time polymerase chain reaction (RT-PCR) and immunocytochemistry. We found that all AFMs reduced cell counts at high concentrations. The highest concentrations with no toxic effect were 100 µM of caffeine, 20 µM of curcumin and 1.1 nM of pirfenidone. The addition of TGF-ß1 to the control medium effectively transformed aCSK into myofibroblasts (MYO-SF), indicated by a 10-fold increase in α-smooth muscle actin (SMA) expression, a 39% decrease in lumican (LUM) expression and a 98% decrease in ALDH3A1 expression (p < 0.001). The concentrations of 100 µM of caffeine, 20/50 µM of curcumin and 1.1 nM of pirfenidone each significantly reduced SMA expression under TGF-ß1 stimulation (p ≤ 0.024). LUM and ALDH3A1 expression remained low under TGF-ß1 stimulation, independently of AFM supplementation. Immunocytochemistry showed that 100 µM of caffeine, 20 µM of curcumin and 1.1 nM of pirfenidone reduce the conversion rate of aCSK to SMA+ MYO-SF. In conclusion, in aCSK, 100 µM of caffeine, 20 µM of curcumin and 1.1 nM of pirfenidone significantly reduced SMA expression and MYO-SF conversion under TGF-ß1 stimulation, with no influence on cell counts. However, the AFMs were unable to protect aCSK from characteristic marker loss.

On the Current Care Situation and Treatment of Ocular Mucous Membrane Pemphigoid in Germany. / Zur Versorgungssituation und konservativen Therapie des okulären vernarbenden Schleimhautpemphigoids in Deutschland.

BACKGROUND: Ocular involvement in mucous membrane pemphigoid (MMP) is relatively rare, with a prevalence of 25 cases per million population, equating to approx. 2,100 patients throughout Germany. Diagnosis can be difficult - especially in cases of isolated ocular involvement - and treatment can be complex and lengthy. Immunosuppressants or immunomodulatory drugs are often used. Due to the complexity of diagnosis and treatment, MMP patients are usually referred to specialized centers. The aim of this project was to evaluate the current care situation of patients with ocular MMP in Germany. METHODS: A paper-based survey was designed and sent to all university eye clinics and other specialized centers in Germany in April 2020. The survey asked about the existence of a specialized outpatient service, the total annual number of patients with MMP, the annual number of newly diagnosed patients, any interdisciplinary collaboration for diagnostic or therapeutic purposes, as well as the local and systemic therapy used. RESULTS: Of a total of 44 clinics, 28 (64%) responded, reporting a total average of 27 ± 42 (0 - 200) patients and 3.6 ± 2.2 (0 - 10) new cases per year. This corresponds to a total of 741 patients. Only nine (32%) of the responding clinics offer specialized MMP clinics. 93% of the centers collaborate with the local dermatology department. 79% perform serological and histological diagnostics in-house. About half of the centers (n = 16) apply a standardized treatment regime. Systemic glucocorticoids (66.7%) are most commonly used, followed by mycophenolate mofetil and dapsone (57.1%), rituximab (33.3%), azathioprine and cyclophosphamide (28.6%), as well as methotrexate (19.0%). The least frequently used treatment is intravenous immunoglobulin (14.3%). CONCLUSION: This survey of German ophthalmology departments obtained data from about one third of the estimated total cohort of all patients with MMP in Germany. These are presumed to be exclusively patients with at least one ocular involvement. The complex care of these patients is usually provided in collaboration with a dermatologist and with the use of systemic anti-inflammatory medication. Currently, an ophthalmological MMP register is being established to better record the epidemiology and care situation of this rare disease in Germany and to improve it in the long term.

Molecular and Functional Characterization of BDNF-Overexpressing Human Retinal Pigment Epithelial Cells Established by Sleeping Beauty Transposon-Mediated Gene Transfer.

More and more patients suffer from multifactorial neurodegenerative diseases, such as age-related macular degeneration (AMD). However, their pathological mechanisms are still poorly understood, which complicates the development of effective therapies. To improve treatment of multifactorial diseases, cell-based gene therapy can be used to increase the expression of therapeutic factors. To date, there is no approved therapy for dry AMD, including late-stage geographic atrophy. We present a treatment option for dry AMD that transfers the brain-derived neurotrophic factor (BDNF) gene into retinal pigment epithelial (RPE) cells by electroporation using the plasmid-based Sleeping Beauty (SB) transposon system. ARPE-19 cells and primary human RPE cells were co-transfected with two plasmids encoding the SB100X transposase and the transposon carrying a BDNF transcription cassette. We demonstrated efficient expression and secretion of BDNF in both RPE cell types, which were further increased in ARPE-19 cell cultures exposed to hydrogen peroxide. BDNF-transfected cells exhibited lower apoptosis rates and stimulated neurite outgrowth in human SH-SY5Y cells. This study is an important step in the development of a cell-based BDNF gene therapy that could be applied as an advanced therapy medicinal product to treat dry AMD or other degenerative retinal diseases.

Efficacy of Topical Administration of Corticosteroids for the Management of Dry Eye Disease: Systematic Review and Meta-Analysis.

The efficacy of corticosteroids (CS) for dry eye disease (DED) has been investigated in the clinical setting. The present study investigated whether topical CS application improves the clinical outcome at last follow-up compared to the baseline. The present study was conducted according to the PRISMA 2020. All the randomized clinical trials (RCTs), which investigated the efficacy of corticosteroids in the management of DED, were accessed. In September 2022, the following databases were accessed: Pubmed, Web of Science, Google Scholar, and Embase. The following data were extracted at baseline and at last follow-up: Ocular Surface Disease Index (OSDI), tear breakup time test (TBUT), Schirmer I test (SIT), and corneal staining. Data from 425 patients were retrieved. A total of 69.4% (295 of 425 patients) were women. CS were effective to improve SIT (p = 0.02) and corneal staining (p = 0.003) at the last follow-up of 10.0 ± 15.3 weeks. TBUT was greater in the CS than in the control group at the last follow-up (p = 0.002). Concluding, topical CS administration led to an increase of SIT and a reduction of corneal staining at a mean of 10 weeks follow-up in patients with DED. Compared to a control group, topical CS administration evidenced greater values of TBUT. Altogether, a good safety profile was witnessed in DED patients receiving CS. However, different safety profiles of different CS formulations were not investigated due to a lack of quantitative data. The exact dosing frequency, duration of therapy, and favorable potency of the CS are still under investigation. Future randomized, controlled trials with larger sample sizes are warranted to provide higher-quality evidence to establish the role of CS in DED.