Immunohistochemical Findings in Retrocorneal Membranes of Eyes with Corneal Decompensation after Complicated Intraocular Surgery.

BACKGROUND: Retrocorneal membranes (RCMs) may result from epithelial ingrowth, stromal keratocytic downgrowth, fibrous metaplasia of the corneal endothelium, or a combination of these processes. In an institutional case series, the clinical history, ocular findings, and immunohistochemical staining results of RCMs were analysed in patients with unilateral corneal decompensation after complicated intraocular surgery. METHODS AND PATIENTS: Between January 2021 and September 2022, six retrocorneal membranes were excised during Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) procedures and classified after screening with haematoxylin and eosin, periodic acid-Schiff, elastic van Gieson staining, and immunohistochemical screening with cytokeratin 7 (CK7), anti-cytokeratin (CAM5.2 and AE1/3), cell surface glycoprotein CD34, smooth muscle actin (α-SMA), and vimentin. RESULTS: On the basis of the immunohistochemical screening, the majority of excised RCMs (5 of 6) could histopathologically be classified as membranes originating from fibrous metaplasia of the corneal endothelium. All these RCMs were positive for CK7, α-SMA, and vimentin and negative for CAM5.2 and CD34. In one patient, an RCM had developed after 18 days of corneal contact to a free-floating dexamethasone implant in the anterior chamber and was classified as originating from stromal keratocyte downgrowth (α-SMA- and vimentin-positive, all others negative). All eyes in this series had a previous history of complicated cataract surgery, partially with subsequent intraocular lens exchange. No eyes after previous penetrating keratoplasty were in this series. CONCLUSIONS: In this series of eyes with previous complicated intraocular interventions (in most cases cataract surgery and revisions), the dominating RCM belonged to the type originating from fibrous metaplasia of the corneal endothelium.

A Short Review on the Safety of Bromphenol Blue for Dye-Assisted Vitreoretinal Interventions.

Bromphenol blue was approved for the intraoperative staining of the vitreous, epiretinal membranes, and internal limiting membrane of the retina several years ago. It has been marketed as a combined dye formulation of bromphenol blue (1.3 mg/mL) and brilliant blue G (0.25 mg/mL). So far, comprehensive information on preclinical and clinical safety data of bromphenol blue is lacking. A PubMed analysis of available literature was performed. Ten relevant publications on preclinical and clinical evaluations of bromphenol blue were found. It is striking that almost no safety data is available on the presently used clinical product. Current clinical use seems not completely be justified by scientific safety data.

A Simple, Inexpensive, and Precise Photographic Method for Intraoperative Toric IOL Alignment.

BACKGROUND: It was the aim of this study to analyse the refractive outcome of toric intraocular lens (t-IOL) implantation guided by a newly developed method of photographic alignment. MATERIAL AND METHODS: Fourteen eyes of 10 patients (6 females, 4 males, age 63.4 ± 6.7 (40.6 - 68.0) years [mean ± 1 SD (range)]) were included in this retrospective study. All eyes received an Oculentis Tplus LS-313 (Oculentis, Berlin, Germany) t-IOL after standard phacoemusification (n = 4) or femtocataract laser-assisted surgery (n = 10). Image-guided t-IOL alignment included: (1) calculation of t-IOL parameters (combination of different biometric methods) and plotting a layout drawing of the target lens position, (2) capture of an anterior segment slit lamp photograph in the upright position, (3)  superposition of the photographs by the t-IOL target plot and a gradual scale, (4) drawing of marker lines on the photograph and removal of the IOL target coordinates, (5) transfer of the final image to a tablet PC, and (6) marking of the target axis at the corneal limbus with an ink pen in the surgical room. RESULTS: Preoperative corneal astigmatism was 2.50 ± 0.97 (1.38 - 4.34) diopters (D) (mean ± 1 SD, range). In all eyes, intraoperative alignment could easily be performed using the photographic target layout. Surgical interventions and postoperative follow-up were without complications in all cases. Residual postoperative astigmatism was 0.16 ± 0.24 (0.00 - 0.75) D (p < 0.001 compared to preoperative astigmatism). In 64% of patients, residual subjective astigmatism was zero, in 93% ≤ 0.5 D, and in 100% ≤ 0.75 D. Postoperative uncorrected logMAR visual acuity (0.05 ± 0.07, range 0.00 - 0.20) and best-corrected visual acuity (0.03 ± 0.05, 0.00 - 0.10) were significantly better (each p < 0.001) than best-corrected preoperative visual acuity (0.21 ± 0.14, 0.00 - 0.49). CONCLUSIONS: Results of this clinical series clearly indicate that the newly developed photographically guided technique of toric lens alignment leads to highly accurate postoperative results for astigmatic correction.

The Assessment of Blood Flow Velocities in Retinal Collaterals in Diabetic Retinopathy.

PURPOSE: Diabetic retinopathy (DR) is a microvascular disease characterized by capillary dropout and resultant retinal ischemia which then leads to retinal vascular remodeling. Our goal was to assess blood flow velocities in retinal collateral vessels in healthy and diabetic subjects with various stages of DR. METHODS: In our pilot study, we enrolled five eyes of five healthy subjects (H), five eyes of four subjects with diabetes and no retinopathy (DM), three eyes of three subjects with mild non-proliferative diabetic retinopathy (MDR), and five eyes of four subjects with proliferative diabetic retinopathy (PDR). Following routine ophthalmic examination, all subjects were imaged using a retinal function imager (RFI; Optical Imaging Inc., Rehovot, Israel). The built-in software of the RFI was used to identify and segment retinal collaterals with measurement of the blood flow velocities (BFV). One-way ANOVA was performed for BFV, followed by Newman-Keuls post hoc test. The level of significance was set at 5%. RESULTS: The total number of collateral segments involved in the study was 30, 31, 21, and 39 in the H, DM, MDR, and PDR groups, respectively. The BFVs in the collaterals were significantly lower in PDR (H: 1.86 ± 0.67, DM: 1.91 ± 0.71, MDR: 1.71 ± 0.53, PDR: 1.37 ± 0.58 mm/s). The PDR group showed a statistically significant difference in the comparisons to all groups (p = 0.012, p = 0.008, and p = 0.043 for the H, DM, and MDR groups, respectively), while no other comparisons between the groups were significant. CONCLUSION: We observed decreased BFV in retinal collaterals in PDR that may be due to the extensive capillary dropout and retinal ischemia. Further studies are needed for the noninvasive functional assessment of retinal microvascular changes in DR to better understand the underlying pathophysiology.

Fluorescein Staining of Intraocular Lenses.

BACKGROUND: Recent case reports have indicated that intraocular lenses may be discoloured by systemically or locally applied fluorescein. Since very few data are available on the susceptibility of intraocular lenses to fluorescein, an experimental survey on lens discolouration was performed. MATERIAL AND METHODS: Intraocular lenses fabricated from polmethylmethacrylate (PMMA), silicone, hydrophobic acrylic copolymers, and hydrophilic acrylic copolymers were exposed to 10% fluorescein. Staining effects were determined by standardised quantification of light transmission. RESULTS: Intraocular lenses fabricated from PMMA, silicone, or hydrophobic acrylic copolymer did not exhibit any measurable dye uptake after exposure to fluorescein. Intensive and rapid discolouration occurred in hydrophilic acrylic intraocular lenses. The transmission of blue light was reduced by 22% after 1 second and by 74% after 10 minutes of dye exposure. CONCLUSIONS: The results indicate that hydrophilic acrylic intraocular lenses develop rapid and intensive discolouration and reduced light transmission after exposure to fluorescein. Lenses fabricated from other materials (PMMA, silicone, hydrophobic acrylic copolymers) were not discoloured by fluorescein staining.

The Use of Optical Coherence Tomography for the Detection of Early Diabetic Retinopathy.

Diabetic retinopathy (DR) is one of the leading causes of vision loss globally with a severe burden on all societies due to its high treatment and rehabilitation costs. The early diagnosis of DR may provide preventive steps (including retinal laser therapy and tight carbohydrate, blood pressure, and cholesterol control) that could in turn help to avoid progression of the pathology with the resultant vision loss. Optical coherence tomography (OCT) enables the in vivo structural imaging of the retina, providing both qualitative (structure) and quantitative (thickness) information. In the past decades, extensive OCT research has been done in the field of DR. In the present review, we are focusing on those that were aiming at detection of the earliest retinal changes before DR could be diagnosed funduscopically. The latest, widely available technology of spectral-domain (SD-)OCT comes with a fast and reliable retinal imaging, which, together with the most recent developments in image processing and artificial intelligence, holds the promise of developing a quick and efficient, state-of-the-art screening tool for DR.

Sustained Benefits of Ranibizumab with or without Laser in Branch Retinal Vein Occlusion: 24-Month Results of the BRIGHTER Study.

PURPOSE: To evaluate the long-term (24-month) efficacy and safety of ranibizumab 0.5 mg administered pro re nata (PRN) with or without laser using an individualized visual acuity (VA) stabilization criteria in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). DESIGN: Phase IIIb, open-label, randomized, active-controlled, 3-arm, multicenter study. PARTICIPANTS: A total of 455 patients. METHODS: Patients were randomized (2:2:1) to ranibizumab 0.5 mg (n = 183), ranibizumab 0.5 mg with laser (n = 180), or laser (with optional ranibizumab 0.5 mg after month 6; n = 92). After initial 3 monthly injections, patients in the ranibizumab with or without laser arms received VA stabilization criteria-driven PRN treatment. Patients assigned to the laser arm received laser at the investigator's discretion. MAIN OUTCOME MEASURES: Mean (and mean average) change in best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) from baseline to month 24, and safety over 24 months. RESULTS: A total of 380 patients (83.5%) completed the study. Ranibizumab with or without laser led to superior BCVA outcomes versus laser (monotherapy and combined with ranibizumab from month 6; 17.3/15.5 vs. 11.6 letters; P < 0.0001). Ranibizumab with laser was noninferior to ranibizumab monotherapy (mean average BCVA change: 15.4 vs. 15.0 letters; P < 0.0001). However, addition of laser did not reduce the number of ranibizumab injections (mean injections: 11.4 vs. 11.3; P = 0.4259). A greater reduction in CSFT was seen with ranibizumab with or without laser versus laser monotherapy over 24 months from baseline (ranibizumab monotherapy -224.7 µm, ranibizumab with laser -248.9 µm, laser [monotherapy and combined with ranibizumab from month 6] -197.5 µm). Presence of macular ischemia did not affect BCVA outcome or treatment frequency. There were no reports of neovascular glaucoma or iris neovascularization. No new safety signals were identified. CONCLUSIONS: The BRIGHTER study results confirmed the long-term efficacy and safety profile of PRN dosing driven by individualized VA stabilization criteria using ranibizumab 0.5 mg in patients with BRVO. Addition of laser did not lead to better functional outcomes or lower treatment need. The safety results were consistent with the well-established safety profile of ranibizumab.

Individualized Ranibizumab Regimen Driven by Stabilization Criteria for Central Retinal Vein Occlusion: Twelve-Month Results of the CRYSTAL Study.

PURPOSE: To assess the 12-month efficacy and safety profile of an individualized regimen of ranibizumab 0.5 mg driven by stabilization criteria in patients with macular edema secondary to central retinal vein occlusion (CRVO). DESIGN: A 24-month, prospective, open-label, single-arm, multicenter study. PARTICIPANTS: Three hundred fifty-seven patients. METHODS: Patients were treated with monthly ranibizumab 0.5-mg injections (minimum of 3 injections) until stable visual acuity (VA) was maintained for 3 consecutive months. Thereafter, ranibizumab 0.5 mg was dosed as needed if monthly monitoring indicated a loss of VA resulting from disease activity. MAIN OUTCOME MEASURES: Mean change from baseline at month 12 in best-corrected VA (BCVA; primary end point) and safety over 12 months. The efficacy of this regimen in subgroups categorized by baseline BCVA score, CRVO duration, or presence of macular ischemia (exploratory analysis). RESULTS: At baseline, the mean BCVA was 53.0 letters and mean CRVO duration was 8.9 months (median, 2.4 months). Ranibizumab 0.5-mg treatment resulted in a statistically significant mean gain in BCVA from baseline at month 12 of 12.3 letters (standard deviation [SD], 16.72 letters; P < 0.0001). The mean number of ranibizumab injections up to month 12 was 8.1 (SD, 2.77). At month 12, mean BCVA gains were similar with or without macular ischemia at baseline (11.6 vs. 12.1 letters); the mean BCVA gain was higher with baseline CRVO duration of less than 3 months (13.4 letters) than with a longer duration (≥3-<9 months, 11.1 letters; ≥9 months, 10.9 letters). Patients with lower baseline BCVA had larger mean BCVA gains at month 12 than those with higher baseline BCVA (≤39/40-59/≥60 and 18.0/12.7/8.9 letters, respectively), although the absolute BCVA at month 12 was higher with higher baseline BCVA. No new ocular or nonocular safety events were observed. CONCLUSIONS: An individualized dosing regimen of ranibizumab 0.5 mg driven by stabilization criteria for up to 12 months resulted in significant BCVA gain in a broad population of patients with macular edema secondary to CRVO, including those with macular ischemia at baseline. The safety findings were consistent with those reported in previous ranibizumab studies in patients with CRVO.

Individualized Stabilization Criteria-Driven Ranibizumab versus Laser in Branch Retinal Vein Occlusion: Six-Month Results of BRIGHTER.

PURPOSE: To compare the 6-month efficacy and safety profile of an individualized stabilization criteria-driven pro re nata (PRN) regimen of ranibizumab 0.5 mg with or without laser versus laser alone in patients with visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). DESIGN: A 24-month, prospective, open-label, randomized, active-controlled, multicenter, phase IIIb study. PARTICIPANTS: A total of 455 patients. METHODS: Eligible patients were randomized 2:2:1 to receive ranibizumab (n = 183), ranibizumab with laser (n = 180), or laser only (n = 92). Patients treated with ranibizumab with or without laser received a minimum of 3 initial monthly ranibizumab injections until visual acuity (VA) stabilization, and VA-based PRN dosing thereafter. In the ranibizumab with laser and laser-only groups, laser was given at the investigator's discretion at a minimum interval of 4 months and if VA was <79 letters. MAIN OUTCOME MEASURES: Mean change from baseline at month 6 in best-corrected visual acuity (BCVA) (primary end point) and central subfield thickness, and safety over 6 months. Exploratory objectives were to evaluate the influence of baseline BCVA, disease duration, and ischemia on BCVA outcomes at month 6. RESULTS: Baseline mean BCVA was 57.7 letters, and mean BRVO duration was 9.9 months. Ranibizumab with or without laser was superior to laser only in improving mean BCVA from baseline at month 6 (14.8 and 14.8 vs. 6.0 letters; both P < 0.0001; primary end point met). Patients with a shorter BRVO duration at baseline had a higher mean BCVA gain than those with a longer BRVO duration. Patients with a poor baseline VA had a better BCVA gain than those with a higher baseline VA, although final BCVA was lower in those with poor baseline VA. In the ranibizumab with or without laser groups, the presence of some macular ischemia at baseline did not influence mean BCVA gains. There were no new ocular or nonocular safety events. CONCLUSIONS: Ranibizumab with an individualized VA-based regimen, with or without laser, showed statistically significant superior improvement in BCVA compared with laser alone in patients with BRVO. Overall, there were no new safety events other than those reported in previous studies.