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.

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.

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.

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.

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 [...].

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.

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.

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.

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.

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.

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.

Elongation of the inferior rectus tendon with fascia lata graft for large vertical squint angles in patients with Graves' orbitopathy.

PURPOSE: To investigate the use of fascia lata (FL) grafts for inferior rectus muscle (IRM) tendon elongation in patients with large vertical squint angles with Graves' orbitopathy (GO). METHODS: In this retrospective study, we included a consecutive series of 20 eyes of 13 patients with GO who underwent IRM tendon elongation with FL. Orthoptic and ophthalmologic examinations including measurement of the head posture, the extent of deviation in primary position (PP), elevation, motility, and binocular diplopia at the tangent of Harms were conducted preoperatively and after a mean postoperative time of 10.8 (5.0-35.0) months in all patients. RESULTS: The mean total repositioning distance was 9.3 ± 3.6 (3.5-16.0) mm. Postoperatively, we found a significant increase in elevation (5.4 ± 2.4 vs. 2.7 ± 2.4 mm preoperatively, p = 0.011). A significant reduction in vertical squint angle (2.8 ± 3.7 vs. 20.2 ± 18.8 Δ preoperatively, p = 0.004), chin elevation (2.3 ± 3.7 vs. 12.9 ± 6.3° preoperatively, p < 0.001), extorsion in PP (0.1 ± 3.8 vs. 8.4 ± 7.8° preoperatively, p = 0.002), and in elevation (1.8 ± 4.8 vs. 11.1 ± 10.9° preoperatively, p = 0.004) occurred postoperatively. A mean dose-effect relation of 2.6 ± 2.9 Δ/mm was calculated. Postoperatively, the lower eyelid retraction was significantly increased (1.5 ± 1.4 vs. 0.4 ± 0.5 mm preoperatively, p = 0.005). CONCLUSION: IRM tendon elongation with FL is a feasible and effective procedure without relevant risk for surgery-related complications.

TREATMENT OF PERSISTENT MACULAR HOLES WITH HEAVY SILICONE OIL.

BACKGROUND/PURPOSE: To determine anatomical success and best-corrected visual acuity after secondary surgery with heavy silicone oil tamponade in patients with persistent full-thickness macular holes. METHODS: In this retrospective study, 63 eyes with persistent full-thickness macular holes after primary pars plana vitrectomy and internal limiting membrane peeling underwent secondary surgery with heavy silicone oil tamponade. Macular spectral domain optical coherence tomography and best-corrected visual acuity measurements were performed during the follow-up. RESULTS: Fifty of 63 eyes (79.4%) achieved anatomical success. In eyes achieving anatomical success, best-corrected visual acuity before primary vitreoretinal surgery was significantly better (0.77 [∼20/125 Snellen] ± 0.24 [1.3-0.3] logarithm of the minimum angle of resolution) compared with eyes not achieving anatomical success (0.88 [∼20/160 Snellen] ± 0.17 [1.1-0.6] logarithm of the minimum angle of resolution, P = 0.044). Minimum linear diameter of full-thickness macular holes was significantly smaller in eyes achieving anatomical success, both before primary (403.4 ± 128.7 [199.0-707.0] µ m vs. 568.1 ± 209.1 [307.0-953.0] µ m, P = 0.009) and secondary surgery (464.1 ± 215.0 [178.0-1,521.0] µ m vs. 663.3 ± 228.5 [451.0-1,301.0] µ m, P = 0.010). Patients remaining phakic during all three surgeries did not benefit from best-corrected visual acuity improvement, although anatomical success was achieved. CONCLUSION: Heavy silicone oil tamponade in secondary surgery for persistent full-thickness macular holes is a safe and efficient surgical method. Best-corrected visual acuity and minimum linear diameter before surgery may be indicators for anatomical success.

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.

Outcomes of combined single-use dual blade goniotomy and cataract surgery.

PURPOSE: Single-use dual blade goniotomy (SBG) is a novel ab interno procedure that removes three to five clock hours of trabecular meshwork (TM). We analysed the reduction of intraocular pressure (IOP) and topical glaucoma medication (Meds) in eyes following combined cataract surgery and SBG (Cat-SBG). METHODS: IOP and Meds were evaluated retrospectively in 55 eyes of 38 patients. 44 eyes had high tension glaucoma (HTG) and eleven eyes had normal tension glaucoma (NTG). Complete success (no Meds) and qualified success (with Meds) for IOP levels ≤ 21, ≤ 18 , ≤ 16 mmHg or ≥ 20% IOP reduction at the two- and six-month follow-up were evaluated. RESULTS: IOP and Meds were significantly reduced from before to two months after Cat-SBG in HTG- and NTG-patients (HTG: IOP 19.4 ± 3.3 to 15.1 ± 3.3 mmHg; p < 0.001; Meds 2.1 ± 1.3 to 0.8 ± 1.3; p < 0.001; NTG: IOP 14.0 ± 2.3 to 11.5 ± 2.3 mmHg; p = 0.004; Meds 1.6 ± 0.7 to 0.3 ± 0.7; p < 0.001). IOP and Meds did not change significantly from two to six months after Cat-SBG. In HTG, complete and qualified success rates were 43% (19/44) and 93% (41/44) for IOP ≤ 18 mmHg, 36% (16/44) and 64% (28/44) for IOP ≤ 16 mmHg and 30% (13/44) and 43% (19/44) for ≥ 20% IOP reduction six months after surgery. In NTG, complete and qualified success was 81% (9/11) and 100% (11/11) for IOP ≤ 18 and ≤ 16 mmHg, and 27% (3/11) for IOP reduction ≥ 20%. IOP and Meds reduction were comparable between HTG and NTG eyes. Only minor postoperative complications occurred. CONCLUSION: Cat-SBG is an efficient method to significantly lower IOP in patients with HTG and NTG.

Human platelet lysate as a replacement for fetal bovine serum in human corneal stromal keratocyte and fibroblast culture.

The isolation and propagation of primary human corneal stromal keratocytes (CSK) are crucial for cellular research and corneal tissue engineering. However, this delicate cell type easily transforms into stromal fibroblasts (SF) and scar inducing myofibroblasts (Myo-SF). Current protocols mainly rely on xenogeneic fetal bovine serum (FBS). Human platelet lysate (hPL) could be a viable, potentially autologous, alternative. We found high cell survival with both supplements in CSK and SF. Cell numbers and Ki67+ ratios increased with higher fractions of hPL and FBS in CSK and SF. We detected a loss in CSK marker expression (Col8A2, ALDH3A1 and LUM) with increasing fractions of FBS and hPL in CSK and SF. The expression of the Myo-SF marker SMA increased with higher amounts of FBS but decreased with incremental hPL substitution in both cell types, implying an antifibrotic effect of hPL. Immunohistochemistry confirmed the RT-PCR findings. bFGF and HGF were only found in hPL and could be responsible for suppressing the Myo-SF conversion. Considering all findings, we propose 0.5% hPL as a suitable substitution in CSK culture, as this xeno-free component efficiently preserved CSK characteristics, with non-inferiority in terms of cell viability, cell number and proliferation in comparison to the established 0.5% FBS protocol.

Association of ocular blood flow and contrast sensitivity in normal tension glaucoma.

PURPOSE: To investigate the relationship of ocular blood flow (via arteriovenous passage time, AVP) and contrast sensitivity (CS) in healthy as well as normal tension glaucoma (NTG) subjects. DESIGN: Mono-center comparative prospective trial METHODS: Twenty-five NTG patients without medication and 25 healthy test participants were recruited. AVP as a measure of retinal blood flow was recorded via fluorescein angiography after CS measurement using digital image analysis. Association of AVP and CS at 4 spatial frequencies (3, 6, 12, and 18 cycles per degree, cpd) was explored with correlation analysis. RESULTS: Significant differences regarding AVP, visual field defect, intraocular pressure, and CS measurement were recorded in-between the control group and NTG patients. In NTG patients, AVP was significantly correlated to CS at all investigated cpd (3 cpd: r = - 0.432, p< 0.03; 6 cpd: r = - 0.629, p< 0.0005; 12 cpd: r = - 0.535, p< 0.005; and 18 cpd: r = - 0.58, p< 0.001), whereas no significant correlations were found in the control group. Visual acuity was significantly correlated to CS at 6, 12, and 18 cpd in NTG patients (r = - 0.68, p< 0.002; r = - 0.54, p< .02, and r = - 0.88, p< 0.0001 respectively), however not in healthy control patients. Age, visual field defect MD, and PSD were not significantly correlated to CS in in the NTG group. MD and PSD were significantly correlated to CS at 3 cpd in healthy eyes (r = 0.55, p< 0.02; r = - 0.47, p< 0.03). CONCLUSION: Retinal blood flow alterations show a relationship with contrast sensitivity loss in NTG patients. This might reflect a disease-related link between retinal blood flow and visual function. This association was not recorded in healthy volunteers.

Effects of uncomplicated Descemet membrane endothelial keratoplasty on the central retinal thickness.

PURPOSE: To determine retinal thickness (RT) changes and the incidence of macular edema after uncomplicated Descemet membrane endothelial keratoplasty (DMEK-ME) in patients without ME risk factors. METHODS: In this retrospective study, 107 pseudophakic eyes of 74 patients with Fuchs endothelial dystrophy (FED) (79.4%) or bullous keratopathy (BK) (20.6%) underwent DMEK surgery between 2016 and 2019 at the Department of Ophthalmology, RWTH Aachen University. Patients with intra- or postoperative complications as well as pre-existing risk factors for ME were excluded. Macular spectral-domain optical coherence tomography (SD-OCT) and best spectacle-corrected visual acuity (BSCVA) measurements were performed before, 1 week, 1 month, and 6 months after surgery. Retinal thickness (RT) was analyzed in the central foveal 1 mm (CSF), parafoveal 3 mm and 6 mm subfield. RESULTS: Eight eyes (7.5%) developed DMEK-ME 1 month after surgery. Six DMEK-ME eyes (75%) were rebubbled, compared with 31.3% (31 of 99; P = 0.02) of the non DMEK-ME eyes. DMEK-ME eyes had a significantly thicker CSF 1 month after surgery (432.0 ± 97.6 µm) compared with non-DMEK-ME eyes (283.7 ± 22.2 µm; P = 0.01). The other subfields and time points showed no significant RT changes. DMEK-ME significantly impaired BSCVA (0.38 ± 0.92 logMAR) only 1 month after surgery in comparison to the non DMEK-ME eyes (0.23 ± 0.87 logMAR, P = 0.015). CONCLUSION: Excluding systemic and surgery-related risk factors, rebubbling increases the risk of DMEK-ME. Performing a CSF scan 1 month after surgery, particularly in rebubbled eyes, efficiently detects DMEK-ME and allows the prompt initiation of treatment, e.g., topical corticosteroid and non-steroidal (NSAID) eye drops.

Does hemispheric vascular regulation differ significantly in glaucoma patients with altitudinal visual field asymmetry? A single-center, prospective study.

PURPOSE: Vascular risk factors and ocular perfusion are heatedly discussed in the pathogenesis of glaucoma. The retinal vessel analyzer (RVA, IMEDOS Systems, Germany) allows noninvasive measurement of retinal vessel regulation. Significant differences especially in the veins between healthy subjects and patients suffering from glaucoma were previously reported. In this pilot-study we investigated if localized vascular regulation is altered in glaucoma patients with altitudinal visual field defect asymmetry. METHODS: 15 eyes of 12 glaucoma patients with advanced altitudinal visual field defect asymmetry were included. The mean defect was calculated for each hemisphere separately (-20.99 ± 10.49 profound hemispheric visual field defect vs -7.36 ± 3.97 dB less profound hemisphere). After pupil dilation, RVA measurements of retinal arteries and veins were conducted using the standard protocol. The superior and inferior retinal vessel reactivity were measured consecutively in each eye. RESULTS: Significant differences were recorded in venous vessel constriction after flicker light stimulation and overall amplitude of the reaction (p < 0.04 and p < 0.02 respectively) in-between the hemispheres. Vessel reaction was higher in the hemisphere corresponding to the more advanced visual field defect. Arterial diameters reacted similarly, failing to reach statistical significance. CONCLUSION: Localized retinal vessel regulation is significantly altered in glaucoma patients with asymmetric altitudinal visual field defects. Veins supplying the hemisphere concordant to a less profound visual field defect show diminished diameter changes. Vascular dysregulation might be particularly important in early glaucoma stages prior to a significant visual field defect.

Intraocular lens power calculation for plus and minus lenses in high myopia using partial coherence interferometry.

PURPOSE: We assessed the accuracy of lens power calculation in highly myopic patients implanting plus and minus intraocular lenses (IOL). METHODS: We included 58 consecutive, myopic eyes with an axial length (AL) > 26.0 mm, undergoing phacoemulsification and IOL implantation following biometry using the IOLMaster 500. For lens power calculation, the Haigis formula was used in all cases. For comparison, refraction was back-calculated using the Barrett Universal II (Barrett), Holladay I, Hill-RBF (RBF) and SRK/T formulae. RESULTS: The mean axial length was 30.17 ± 2.67 mm. Barrett (80%), Haigis (87%) and RBF (82%) showed comparable numbers of IOLs within 1 diopter (D) of target refraction. Visual acuity (BSCVA) improved (p < 0.001) from 0.60 ± 0.35 to 0.29 ± 0.29 logMAR (> 28-days postsurgery). The median absolute error (MedAE) of Barrett 0.49 D, Haigis 0.38, RBF 0.44 and SRK/T 0.44 did not differ. The MedAE of Haigis was significantly smaller than Holladay (0.75 D; p = 0.01). All median postoperative refractive errors (MedRE) differed significantly with the exception of Haigis to SRK/T (p = 0.6): Barrett - 0.33 D, Haigis 0.25, Holladay 0.63, RBF 0.04 and SRK/T 0.13. Barrett, Haigis, Holladay and RBF showed a tendency for higher MedAEs in their minus compared to plus IOLs, which only reached significance for SRK/T (p = 0.001). Barrett (p < 0.001) and RBF (p = 0.04) showed myopic, SRK/T (p = 002) a hyperopic shift in their minus IOLs. CONCLUSIONS: In highly myopic patients, the accuracies of Barrett, Haigis and RBF were comparable with a tendency for higher MedAEs in minus IOLs. Barrett and RBF showed myopic, SRK/T a hyperopic shift in their minus IOLs.