Asymmetric response to ranibizumab in mixed choroidal neovascularization in a neovascular age-related macular degeneration diagnosed on OCT angiography - case report.

BACKGROUND: To present a case report of a patient with a mixed choroidal neovascular membrane (CNV) with an asymmetric response to ranibizumab diagnosed on optical coherence tomography angiography (OCTa). CASE PRESENTATION: A 61-year-old male was referred to our department in September 2017 due to decreased vision in his left eye. Best-corrected visual acuity (BCVA) was 43 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the left eye. Macular edema was present in the left eye, and a mixed CNV was identified on the OCTa. Therapy with intravitreal ranibizumab was commenced. After 5 ranibizumab injections, the BCVA was 42 ETDRS letters, and considerable intraretinal edema was still present. OCTa showed a resolution of the type 2 lesion of the mixed CNV; however, the type 1 lesion had continued to grow. The patient was then switched to intravitreal aflibercept. After 3 monthly aflibercept injections, the BCVA improved to 53 ETDRS letters, and a reduction of the edema was observed on the optical coherence tomography (OCT). OCTa showed a decrease in both the area and vessel density in the type 1 lesion of the CNV. Therapy with aflibercept was continued; however, while the intraretinal edema continued to improve, atrophy developed in the macula and the BCVA worsened to 43 ETDRS letters. CONCLUSIONS: Ranibizumab nonresponse in a neovascular age-related macular degeneration is not uncommon. However, to our knowledge, this is the first described case of an asymmetric response to ranibizumab in a mixed CNV. While the type 2 lesion of the CNV reacted swiftly to the ranibizumab therapy, the type 1 lesion continued to grow. As with some other cases of ranibizumab resistance, switching to aflibercept proved effective.

Macular telangiectasia type 2 accompanied by solitary retinal astrocytic hamartoma (case report).

BACKGROUND: To present a coincidence of macular telangiectasia type 2 and solitary retinal astrocytic hamartoma in one patient. CASE PRESENTATION: A 50-year-old woman was examined in the Department of Ophthalmology of University hospital Kralovske Vinohrady for complaints of metamorphopsia in her left eye. Her uncorrected visual acuity (VA) was 4/4 on Early Treatment Diabetic Retinopathy Study charts (ETDRS), on the retina of her left eye white, prominent, partially calcified tumour 1 disc diameter in diameter, 1,5 disc diameter from the foveola was detected on the retina. In the macular region of both eyes, parafoveal greying with crystalline deposits and changes in retinal vasculature were visible. We performed following examinations: fluorescein angiography (FA), B-scan ultrasound, spectral domain optical coherence tomography (SD-OCT) including photo documentation. FA showed partial hyperfluorescence of mulberry-like surface of the tumour typical for retinal astrocytic hamartoma. Parafoveally in both eyes, leakage from parafoveal telangiectasia was apparent. SD-OCT showed cystoid space in the macular region of both eyes as well as changes in inner and outer photoreceptor segment junction in left eye. SD-OCT of the tumour showed proliferation in retinal nerve fibre layer with normal structure of underlying retinal layers and choroid. Ultrasound examination of the tumour detected solid, highly echogenic prominent tumour with high reflectivity and acoustic shadow. CONCLUSION: A coincidence of two relatively rare clinical units, macular telangiectasia type 2 and solitary astrocytic hamartoma was detected as a unique and rare observation.

Serum autoantibodies against hexokinase 1 manifest secondary to diabetic macular edema onset.

AIMS: Autoantibodies against hexokinase 1 (HK1) were recently proposed to be associated with diabetic macular edema (DME). We hypothesized that anti-HK1 autoantibodies can be used as DME markers and to predict DME onset. MATERIALS AND METHODS: Serum from patients with 1) DME, 2) diabetes mellitus (DM), 3) allergies or autoimmunities, and 4) control subjects was tested for anti-HK1 and anti-hexokinase 2 (HK2) autoantibodies by immunoblotting. Patients with DM were prospectively followed for up to nine years, and the association of anti-HK1 antibodies with new-onset DME was evaluated. The vitreous humor was also tested for autoantibodies. RESULTS: Among patients with DME, 32 % were positive for anti-HK1 autoantibodies (42 % of those with underlying type 1 DM and 31 % of those with underlying type 2 DM), and 12 % were positive for anti-HK2 autoantibodies, with only partial overlap of these two groups of patients. Anti-HK1 positive were also 7 % of patients with DM, 6 % of patients with allergies and autoimmunities, and 3 % of control subjects. The latter three groups were anti-HK2 negative. Only one of seven patients with DM who were initially anti-HK1 positive developed DME. CONCLUSIONS: Anti-HK1 autoantibodies can be used as DME markers but fail to predict DME onset.

Biosimilar candidate CT-P42 in diabetic macular edema: 24-week results from a randomized, active-controlled, Phase III study.

OBJECTIVE: To demonstrate the therapeutic similarity of CT-P42 compared to reference aflibercept (Eylea®) in adult patients with diabetic macular edema (DME). DESIGN: Randomized, active-controlled, double-masked, Phase III clinical trial PARTICIPANTS: Patients with a diagnosis of either type 1 or 2 diabetes mellitus (DM) with DME involving the center of the macula. METHODS: Patients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.05 mL) by intravitreal injection every 4 weeks (5 doses) then every 8 weeks (4 doses) in the main study period. Results up to Week 24 are reported herein. MAIN OUTCOME MEASURES: The primary endpoint was mean change from baseline at Week 8 in best corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Equivalence between CT-P42 and reference aflibercept was to be concluded if the two-sided 95% confidence interval (CI) (global assumptions) and two-sided 90% CI (US Food and Drug Administration [FDA] assumptions) for the treatment difference fell entirely within the equivalence margin of ±3 letters, as assessed in the full analysis set. RESULTS: Overall, 348 patients were randomized (CT-P42: 173; reference aflibercept: 175). BCVA improved from baseline to Week 8 in both groups, with a least squares mean (standard error) improvement of 9.43 (0.798) and 8.85 (0.775) letters in the CT-P42 and reference aflibercept groups, respectively. The estimated between-group treatment difference was 0.58 letters, with the CIs within the pre-defined equivalence margin of ±3 letters (95% CI -0.73, 1.88 [global]; 90% CI -0.52, 1.67 [FDA]). Through Week 24, other efficacy results for the two groups, in terms of change in BCVA and retinal central subfield thickness, as well as ETDRS Diabetic Retinopathy Severity Scale score, supported therapeutic similarity. Pharmacokinetics, usability, safety (including the proportions of patients experiencing at least one treatment-emergent adverse event [CT-P42: 50.3%; reference aflibercept: 53.7%]), and immunogenicity were also comparable between groups. CONCLUSIONS: This study in patients with DME demonstrated equivalence between CT-P42 and reference aflibercept (2 mg/0.05 mL) in terms of efficacy, with similar pharmacokinetic, usability, safety, and immunogenicity profiles.

Biosimilar SB11 versus reference ranibizumab in neovascular age-related macular degeneration: 1-year phase III randomised clinical trial outcomes.

BACKGROUND/AIMS: To provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD). METHODS: Setting: Multicentre. Design: Randomised, double-masked, parallel-group, phase III equivalence study. Patient population: ≥50 years old participants with nAMD (n=705), one 'study eye'. INTERVENTION: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ. Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks. RESULTS: Baseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was -0.6 letters (90% CI -2.1 to 0.9) and of change from baseline in central subfield thickness was -14.9 µm (95% CI -25.3 to -4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively. CONCLUSIONS: Longer-term results of this study further support the biosimilarity established between SB11 and RBZ.

Efficacy and Safety of the Aflibercept Biosimilar SB15 in Neovascular Age-Related Macular Degeneration: A Phase 3 Randomized Clinical Trial.

Importance: Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy. Objective: To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD). Design, Setting, and Participants: This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up. Intervention: Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56. Main Outcomes and Measures: The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity. Results: The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 µm vs AFL, -115.7 µm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable. Conclusions and Relevance: In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD. Trial Registration: ClinicalTrials.gov Identifier: NCT04450329.

Biosimilar SB15 versus reference aflibercept in neovascular age-related macular degeneration: 1-year and switching results of a phase 3 clinical trial.

BACKGROUND/AIMS: To evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular degeneration (nAMD). DESIGN: Prospective, double-masked, randomised, phase 3 trial. METHODS: Participants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch's membrane). Additional endpoints included safety, PK and immunogenicity. RESULTS: Efficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (-2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were -119.2 µm and -132.4 µm for SB15/SB15 and -126.6 µm and -136.3 µm for AFL/AFL, respectively (CST: difference (95% CI)=7.4 µm (-6.11 to 20.96); TRT: difference (95% CI)=3.9 µm (-18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (-2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups. CONCLUSIONS: Efficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants.

Incidence of adverse events after loading phase of the brolucizumab therapy of neovascular AMD: Real-life evidence in the Czech Republic.

AIM: To evaluate the incidence of ocular adverse events after loading phase of the brolucizumab therapy in patients with neovascular age-related macular degeneration (nAMD) in real-life clinical practice - in treatment-naive patients and in patients after switching from another anti-VEGF agent. Another aim was to evaluate treatment outcomes in patients with adverse events. METHODS: This is a multicentre, retrospective, observational study from 16 application centres in the Czech Republic. Patients diagnosed with nAMD were treated with brolucizumab in a fixed regimen of loading phase (3 injections administered at one-month intervals) and the mean follow-up period was 120 ± 10 days after the first injection. The incidence of adverse events and the development of best corrected visual acuity (BCVA) and central retinal thickness (CRT) in patients with complications were evaluated. A total of 1,098 eyes were followed up, of which 783 were treatment-naive and 315 eyes were after switching from another anti-VEGF agent. RESULTS: Adverse events were recorded in 42 eyes (3.83%), of which 30 eyes were treatment-naive (2.7%) and 12 eyes were post-switch (1.09%). The mean baseline BCVA ± SD was 56.7 ± 10.7 ETDRS chart letters in the group of patients with adverse events, 58.8 ± 10.1 letters in treatment-naive patients, and 51.4 ± 10.2 letters in patients after switch from another anti-VEGF agent. The mean baseline CRT ± SD was 432.2 ± 154.7 µm, being 435.8 ± 137.3 µm in treatment-naive patients and 424.5 ± 186.6 µm in patients after switch from another anti-VEGF agent. At the end of the follow-up, the mean BCVA ± SD was 53.4 ± 9.5 ETDRS charts letters in patients with adverse events, 55.6 ± 10 letters in treatment-naive patients, and 47.6 ± 10 letters in patients after switching from another anti-VEGF agent. The mean CRT ± SD at the end of the follow-up was 300.7 ± 115.7 µm in the total patient cohort, 285.2 ± 78.8 µm in treatment-naive patients and 334.5 ± 165.4 µm in patients after switching from another anti-VEGF agent. CONCLUSION: We observed the development of adverse events in the form of intraocular inflammation or vasculitis with subsequent decrease in BCVA in 3.83% of cases after loading phase of the brolucizumab therapy. The decrease in BCVA was reversible in most cases after initiation of anti-inflammatory steroid treatment. From a functional and morphological point of view, we did not demonstrate any statistically significant difference between the groups of treatment-naive patients and patients after switching from another anti-VEGF agent.

Early disruption of photoreceptor cell architecture and loss of vision in a humanized pig model of usher syndromes.

Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and there are no suitable animal models for testing therapeutic strategies of the ocular constituent of USH, so far. By introducing a human mutation into the harmonin-encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction, and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis, and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Fibroblasts from USH1C pigs or USH1C patients showed significantly elongated primary cilia, confirming USH as a true and general ciliopathy. Primary cells also proved their capacity for assessing the therapeutic potential of CRISPR/Cas-mediated gene repair or gene therapy in vitro. AAV-based delivery of harmonin into the eye of USH1C pigs indicated therapeutic efficacy in vivo.

Long-term Results of a Combined Procedure of Cataract Surgery and Descemet Membrane Endothelial Keratoplasty With Stromal Rim.

PURPOSE: To evaluate the long-term results of combining cataract surgery, intraocular lens (IOL) implantation, and Descemet membrane endothelial keratoplasty with peripheral stromal support (DMEK-S). METHODS: The outcomes of 107 eyes of 37 patients who had undergone a combination of cataract surgery, IOL implantation, and DMEK-S between October 2007 and February 2015 were retrospectively evaluated. The average follow-up duration was 18.2 ± 18.3 months (range, 6-84 months). Changes in uncorrected and corrected distance visual acuity, spherical equivalent, and corneal endothelial cell density were analyzed. Intraoperative and postoperative complications were also recorded. RESULTS: The mean logMAR uncorrected distance visual acuity improved from 0.92 ± 0.60 preoperatively to 0.33 ± 0.33, 0.28 ± 0.25, 0.24 ± 0.20, and 0.27 ± 0.27 at 6, 12, 24, and 36 months postoperatively (P < 0.001), respectively. The mean logMAR corrected distance visual acuity improved from 0.62 ± 0.65 preoperatively to 0.17 ± 0.29, 0.13 ± 0.21, 0.07 ± 0.16, and 0.11 ± 0.23 at 6, 12, 24, and 36 months postoperatively (P < 0.001), respectively. The mean endothelial cell density decreases were 50.7% ± 21.1%, 50.8% ± 19.8%, 60.7% ± 16.6%, 62.2% ± 11.8%, and 61.8% ± 20.0% at 6, 12, 24, 36, and 48 months after surgery, respectively. Similar trends, although with slightly better visual outcomes, were found in the subgroup of patients without other eye diseases. The mean final deviation from intended spherical equivalent was 0.77 ± 1.19 D, representing a hyperopic shift. CONCLUSIONS: A combined procedure of cataract surgery, IOL implantation, and DMEK-S is an effective method of treatment in patients with combined corneal disease and cataract, maintaining visual rehabilitation in the long term. Future developments should be performed to minimize the incidence of complications.

Two-year results of a combined regimen of aflibercept treatment in three types of choroidal neovascular membrane in the wet form of age-related macular degeneration: Real-life evidence in the Czech Republic.

AIM: To present the results of a 2-year therapy with aflibercept in real-life practice in a mixed regimen in patients with a neovascular form of age-related macular degeneration (nAMD) and to evaluate the treatment response of various types of choroidal neovascular membranes (CNV) - occult (Type 1), classic (Type 2) and minimally classic (Type 4). METHODS: This was a multicentric, prospective, observational study of a series of cases. Patients diagnosed with the wet form of AMD were treated in a fixed regimen (3 injections at intervals of 1 month and then injections at 8-week intervals) in the first year, and in a pro re nata regimen (PRN) in the second year. The period of investigation was 24 months. The development of the best corrected visual acuity (BCVA) was evaluated by means of ETDRS optotypes (Early Treatment Diabetic Retinopathy Study) and the central retinal thickness (CRT). Measurements were performed prior to the commencement of therapy and then after 4, 8, 12, 16, 20 and 24 months. RESULTS: The therapeutically naïve group consisted of 135 eyes of 135 patients. Sixty-one eyes suffered from CNV of the 1st type, 50 eyes from CNV of the 2nd type and 24 eyes from CNV of the 4th type. The average baseline of BCVA ± SD in Type 1 CNV was 56.1 ± 10.8 letters of ETDRS, and then, respectively, 62.2 ± 12.9 letters, 62.8 ± 15.1 letters and 59.4 ± 13.2 letters after 4, 12 and 24 months. The average baseline value of CRT ± SD for Type 1 CNV was 442.4 ± 194.9 µm, and then 302.5 ± 144.4 µm, 277.7 ± 106.5 µm and 327.6 ± 138.6 µm at months 4, 12 and 24. The average baseline value of BCVA ± SD in Type 2 CNV was 55.6 ± 9.9 letters of ETDRS, and then 62.5 ± 11.1 letters, 62.5 ± 14.2 letters and 60.6 ± 15.1 letters after 4, 12 and 24 months. The average baseline value of CRT ± SD in Type 2 CNV was 446.8 ± 159.1 µm, and then 327.4 ± 127.0 µm, 316.7 ± 139.1 µm and 352.5 ± 132.4 µm at 4, 12 and 24 months. In Type 4 CNV, the average baseline value of BCVA ± SD was 56.7 ± 9.0 letters of ETDRS, and then 59.1 ± 10.6 letters, 59.2 ± 12.6 letters and 58 ± 8.8 letters after 4, 12 and 24 months. The average baseline value of CRT ± SD in Type 4 CNV was 492.1 ± 187.0 µm, and then 333.3 ± 137.5 µm, 326.7 ± 122.4 µm and 328.4 ± 132 µm at months 4, 12 and 24. All these changes were statistically significant (p < 0.05). CONCLUSION: Therapy with aflibercept in a mixed regimen in patients with the wet form of AMD during the investigation resulted in a statistically significant improvement in BCVA and decrease in CRT in both the occult and classic type of CNV. Both the functional and anatomical response to therapy was worse in the minimally classic type (Type 4) of CNV. SUMMARY DECLARATION: Patients suffering from the neovascular form of age-related macular degeneration were treated with aflibercept in a mixed regimen (fixed in the first year and PRN in the second year). After 24 months of examination, a significant improvement of both morphological and functional results was observed in three types of choroidal neovascular membrane.

Efficacy and Safety of a Proposed Ranibizumab Biosimilar Product vs a Reference Ranibizumab Product for Patients With Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial.

Importance: Neovascular age-related macular degeneration is the leading cause of blindness in individuals 50 years or older. The availability of a ranibizumab biosimilar product (SB11) may facilitate access to an effective alternative to this treatment. Objective: To demonstrate equivalence of efficacy, similar safety, and similar immunogenicity of SB11 compared with the reference ranibizumab. Design, Setting, and Participants: This randomized, double-masked, parallel-group phase 3 equivalence study was conducted in 75 centers in 9 countries from March 14, 2018, to December 9, 2019, among 705 participants 50 years or older with neovascular age-related macular degeneration with active subfoveal choroidal neovascularization lesions. Analysis was performed on an intent-to-treat basis. Interventions: Intravitreous injection of SB11 or ranibizumab, 0.5 mg, every 4 weeks through week 48. Main Outcomes and Measures: Preplanned interim analysis after all participants completed the week 24 assessment of primary efficacy end points at week 8 for change from baseline in best-corrected visual acuity (BCVA) and week 4 for central subfield thickness (CST), with predefined equivalence margins for adjusted treatment differences of -3 letters to 3 letters for BCVA and -36 µm to 36 µm for CST. Results: Baseline and disease characteristics among 705 randomized participants (403 women [57.2%]; mean [SD] age, 74.1 [8.5] years) were comparable between treatment groups (SB11, 351; ranibizumab, 354). Least-squares mean (SE) changes in BCVA from baseline at week 8 were 6.2 (0.5) letters in the SB11 group vs 7.0 (0.5) letters in the ranibizumab group, with an adjusted treatment difference of -0.8 letter (90% CI, -1.8 to 0.2 letters). Least-squares mean (SE) changes in CST from baseline at week 4 were -108 (5) µm in the SB11 group vs -100 (5) µm in the ranibizumab group, with an adjusted treatment difference of -8 µm (95% CI, -19 to 3 µm). Incidences of treatment-emergent adverse events (231 of 350 [66.0%] vs 237 of 354 [66.9%]), including serious treatment-emergent adverse events (44 of 350 [12.6%] vs 44 of 354 [12.4%]) and treatment-emergent adverse events leading to study drug discontinuation (8 of 350 [2.3%] vs 5 of 354 [1.4%]), were similar in the SB11 and ranibizumab groups. Immunogenicity was low, with a cumulative incidence of antidrug antibodies up to week 24 of 3.0% (10 of 330) in the SB11 group and 3.1% (10 of 327) in the ranibizumab group. Conclusions and Relevance: These findings of equivalent efficacy and similar safety and immunogenicity profiles compared with ranibizumab support the use of SB11 for patients with neovascular age-related macular degeneration. Trial Registration: ClinicalTrials.gov Identifier: NCT03150589.

Descemet membrane endothelial keratoplasty with stromal rim (DMEK-S) in complicated patients.

PURPOSE: To evaluate the outcomes of the hybrid technique of posterior lamellar keratoplasty (Descemets' membrane endothelial keratoplasty with stromal rim, DMEK-S) in eyes with multiple ocular pathologies. METHODS: A retrospective case control study of the consecutive group of all eyes with combined ocular pathologies which underwent DMEK-S keratoplasty. We evaluated the number of pre- and post-operative complications; uncorrected distance visual acuity (UDVA); corrected distance visual acuity (CDVA) and endothelial cell density (ECD). The first group (Group 1 - 100 eyes) was compared to a control group of eyes (Group 2 - 145 eyes) without combined ocular pathologies, which were operated throughout the same time period. Comparisons were made in the 12th month of the follow-up. RESULTS: Both the UDVA and the CDVA statistical values 12 months after the surgery were significantly better in Group 2. ECD was comparable in both groups. The number of complications during surgery was considerably higher in Group 1, where a certain type of complication occurred in 15 eyes (15%), while in Group 2 this complication occurred only in 9 eyes (6.2%). In Group 1 a slightly higher number of rebubbling cases (52% vs. 48.3%) occurred, as well as more than twice as many cases of primary graft failure (34% vs. 15.7%) compared to Group 2. CONCLUSION: DMEK-S - hybrid endothelial transplantation in complicated eyes in the evaluated group of patients led to a noticeable improvement of visual acuity. When compared to surgeries in uncomplicated eyes, DMEK-S results in a higher rate of postoperative complications, especially graft detachment and primary failure.

25-gauge vitrectomy and gas for the management of rhegmatogenous retinal detachment.

AIMS: To evaluate the anatomical and functional results in patients with rhegmatogenous retinal detachment (RRD) who underwent 25-gauge pars plana vitrectomy (PPV) with gas tamponade. MATERIALS AND METHODS: A retrospective evaluation of 126 eyes of 126 patients (79 men, 47 women) with RRD who underwent 25-gauge PPV with gas tamponade (13% C3F8 in 87 eyes, 20% SF6 in 39 eyes). 113 patients (89.7%), were operated on under local anaesthesia, 13 patients (10.3%) under general anaesthesia. Macula was detached in 85 eyes (67.5%). 53 eyes had pseudophakic RRD, 73 eyes were phakic. Anatomical success of the primary intervention, change in best corrected visual acuity (BCVA) and incidence of complications were assessed. An average follow-up period is 7.2 months (6-15). RESULTS: With single operation, retinal attachment was achieved in 125 eyes (99.2%); the final anatomical success was 100%. The initial mean BCVA was 0.89 logMar (2.00 to 0.00); at the end of the follow-up period, it improved to 0.23logMAR (1.00 to -0.10), P < 0,0001. During the first post-intervention day, hypotony of the eye below 10 mmHg was observed in 1 patient (0.8%); on the contrary, intraocular pressure was temporarily increased to 25 mmHg and more in 36 patients (28.6%). CONCLUSION: The surgical treatment of RRD using 25-gauge PPV with expansive gas tamponade renders excellent anatomical results and improvement in BCVA. The incidence of complications and necessity of sclerotomy suturing are low.

Response to Aflibercept Therapy in Three Types of Choroidal Neovascular Membrane in Neovascular Age-Related Macular Degeneration: Real-Life Evidence in the Czech Republic.

PURPOSE: To present a cohort of treatment-naive patients with the neovascular form of age-related macular degeneration (nAMD) treated with aflibercept in a fixed regimen and evaluate the treatment response of three types of choroidal neovascular membrane (CNV)-occult (Type 1), classic (Type 2), and minimally classic (Type 4). METHODS: This was a multicentre, prospective, observational consecutive case series study. Patients diagnosed with three types of CNV of nAMD were treated in a fixed regimen (3 injections every 4 weeks, and then injections at 8 week intervals). The follow-up period was 48 weeks. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured using Early Treatment Diabetic Retinopathy Study (ETDRS) charts and spectral-domain optical coherence tomography (OCT). The measurements were taken at the baseline and then at 16, 32, and 48 weeks. RESULTS: The treatment-naive group was composed of 135 eyes of 135 patients in the study. 61 eyes had Type 1 lesions of CNV, 50 eyes had Type 2 lesions, and 24 eyes had Type 4 lesions. Mean baseline BCVA ± SD for Type 1 lesions was 56.1 ± 10.8 ETDRS letters, and then 62.2 ± 12.9 letters, 61.2 ± 13.7 letters, and 62.8 ± 15.1 letters at 16, 32, and 48 weeks, respectively. Mean baseline CRT ± SD for Type 1 lesions was 442.4 ± 194.9 µm, and then 302.5 ± 144.4 µm, 299.7 ± 128.5 µm, and 277.7 ± 106.5 µm at 16, 32, and 48 weeks, respectively. Mean baseline BCVA ± SD for Type 2 lesions was 55.6 ± 9.9 ETDRS letters, and then 62.5 ± 11.1 letters, 60.7 ± 13.0 letters, and 62.5 ± 14.2 letters at 16, 32, and 48 weeks, respectively. Mean baseline CRT ± SD. For Type 4 lesions mean baseline BCVA ± SD was 56.7 ± 9.0 ETDRS letters, and then 59.1 ± 10.6 letters, 59.5 ± 11.4 letters, and 59.2 ± 12.6 letters at 16, 32, and 48 weeks respectively. Mean baseline CRT ± SD for Type 4 lesions was 492.1 ± 187.0 µm, and then 333.3 ± 137.5 µm, 354.4 ± 175.0 µm, and 326.7 ± 122.4 µm at 16, 32, and 48 weeks respectively. All these changes were statistically significant (p < 0.005). CONCLUSIONS: The primary outcome of our study is that the treatment with aflibercept in nAMD patients led to statistically significant improvement in BCVA and to a decrease in CRT throughout the follow-up period in both occult and classic types of CNV. The minimally classic type of CNV demonstrated a poorer functional and anatomical response to treatment.

The Burden of Macular Diseases in Central and Eastern Europe-Implications for Healthcare Systems.

BACKGROUND: Despite the significant impact of retinal diseases such as wet age-related macular degeneration (wAMD) and diabetic macular edema (DME), there is a limited understanding of how these conditions are managed in Central and Eastern Europe (CEE). OBJECTIVES: To provide a comprehensive overview of the clinical and economic burden of wAMD and DME in CEE and the status quo associated with their management. METHODS: A narrative literature review was undertaken to identify existing data on wAMD and DME, including epidemiology, economic burden, clinical guidelines, and available and reimbursed treatments. Data were collected from relevant sources such as PubMed, ophthalmology associations, national statistical offices, and government agency websites; practical viewpoints were provided by local ophthalmologists and healthcare economics experts in CEE. RESULTS: Epidemiological data on wAMD and DME are limited in CEE, and intercountry comparison is difficult because of differences in data collection methodologies. There are effective treatment options for wAMD and DME, and international guidelines advocate the use of intravitreal anti-vascular endothelial growth factor injections as first-line therapy. Local expert organizations broadly support these recommendations; nevertheless, no clinical practice guidelines exist on the treatment of wAMD and DME in CEE. Access to and reimbursement of anti-vascular endothelial growth factor agents vary significantly in the region and, as a result, many patients remain untreated or inadequately treated. CONCLUSIONS: There is an urgent need for the creation of a wAMD/DME treatment program in CEE to ensure that patients have timely access to the most appropriate treatments.