Decline In Best-corrected Visual Acuity Research Articles

Clinical, Ophthalmic and Genetic Characterization of RPGRIP1-Associated Leber Congenital Amaurosis/Early Onset Severe Retinal Dystrophy

PurposeTo present the clinical characteristics, retinal features, natural history, and genetics of RPGRIP1-Associated Early Onset Severe Retinal Dystrophy (EOSRD)/Leber Congenital Amaurosis (LCA). DesignRetrospective case series. MethodsReview of clinical notes, multi-modal retinal imaging, and molecular diagnosis of 18 patients (17 families) with EOSRD/LCA and disease-causing variants in RPGRIP1. ResultsThe mean age of visual symptoms onset was 0.87 ± 1 year (birth-3 years) and the mean age at baseline visit was 11.4 ± 10.2 years (1-39 years). At the baseline visit, 44% of patients were legally blind (range= 2-39 years) and there was no significant association found between age and best corrected visual acuity (BCVA) in cross sectional analysis. Retinal evaluation showed an abolished electroretinogram or a cone-rod dystrophy pattern, none or minimal pigment deposits, a hyperautofluorescent ring at the posterior pole, and a largely preserved central macular architecture, with retained outer nuclear layer and ellipsoid zone island into adulthood. Eleven variants (48%) were previously unreported, and 13 families (76%) had a double null genotype (DN). Twelve patients (67%) had follow up assessments over a 15.7 ± 9.5 year period. The rate of BCVA decline was 0.02 LogMAR (1 letter)/year. ConclusionsRPGRIP1-EOSRD/LCA often presents at birth or early infancy, with nystagmus, decreased VA, hyperopia, and photophobia. Patients with a DN genotype may develop symptoms earlier and have worse vision. Multimodal imaging may show a hyperautofluorescent posterior pole ring, and relatively preserved central macular architecture, suggesting that the condition is a promising candidate for gene supplementation.

An Investigation of Keratoplasty Procedures and Their Outcomes in Iraq

Introduction: The treatment of corneal disorders involves the use of various forms of keratoplasty. The objective of this study was to provide a detailed description of the various types of keratoplasty procedures performed in Iraq, as well as their corresponding outcomes.
 Methods: An observational study was conducted at Al-Zahraa Teaching Hospital to document cases of keratoplasty. The collected data included age, gender, types of keratoplasty, indications, previous surgical or medical history, and postoperative outcomes. The types of keratoplasty included penetrating keratoplasty (PKP), deep anterior lamellar keratoplasty (DALK), and Descemet's stripping endothelial keratoplasty (DSEK). Additionally, we performed cataract surgery and intraocular lens (IOL) insertion for those with cataracts, using either IOLs with scleral fixation or IOLs with iris fixation. We complete the task on the first day following the purchase order, then the first week, the first month, and every six months thereafter. Prior to surgery, patients with corneal vascularization had laser photocoagulation of the blood vessels in the cornea.
 Results: Ages range from 4 to 90. People over 40 (60.8%) were the most common age group. The female prevalence was 52.9%. Right-eye illness was diagnosed 51.6% of the time. 60% of patients underwent PKP. 26.8% had DALK, 12.4% had DSEK. Post keratoplasty, the statistically-significant improvement-ratio was 68.5% as eyes best corrected visual acuity (BCVA) improvement, while 12.2% of eyes showed a decline in BCVA and 19.3% discharged with no changes in BCVA. Postoperatively, BCVA was significantly lower in cases with a duration below 1 year (1.5), and better among the duration > 3 years (0.5). The greatest improvements were seen in cases with infective keratitis (-0.7), corneal dystrophies (-0.6), and advanced keratoconus (-0.7) whereas the lowest rates were documented in cases with a graft rejection (-0.3), and bullous keratopathy (-0.3)
 Conclusion: Keratoplasty is associated with a substantial enhancement of visual acuity in the younger population. Infective keratitis, keratoconus, and corneal dystrophy produce the most optimal and superior results. The PKP method is the most frequently performed.

Outcomes and Complications of Limbal Stem Cell Allograft Transplantation: A Report by the American Academy of Ophthalmology

To review the published literature on the safety and outcomes of keratolimbal allograft (KLAL) transplantation and living-related conjunctival limbal allograft (lr-CLAL) transplantation for bilateral severe/total limbal stem cell deficiency (LSCD). Literature searches were last conducted in the PubMed database in February 2023 and were limited to the English language. They yielded 523 citations; 76 were reviewed in full text, and 21 met the inclusion criteria. Two studies were rated level II, and the remaining 19 studies were rated level III. There were no level I studies. After KLAL surgery, best-corrected visual acuity (BCVA) improved in 42% to 92% of eyes at final follow-up (range, 12-95 months). The BCVA was unchanged in 17% to 39% of eyes and decreased in 8% to 29% of eyes. Two of 14 studies that evaluated the results of KLAL reported a notable decline in visual acuity over time postoperatively. Survival of KLAL was variable, ranging from 21% to 90% at last follow-up (range, 12-95 months) and decreased over time. For patients undergoing lr-CLAL surgery, BCVA improved in 31% to 100% of eyes at final follow-up (range, 16-49 months). Of the 9 studies evaluating lr-CLAL, 4 reported BCVA unchanged in 30% to 39% of patients, and 3 reported a decline in BCVA in 8% to 10% of patients. The survival rate of lr-CLAL ranged from 50% to 100% at final follow-up (range, 16-49 months). The most common complications were postoperative elevation of intraocular pressure, persistent epithelial defects, and acute allograft immune rejections. Given limited options for patients with bilateral LSCD, both KLAL and lr-CLAL are viable choices that may provide improvement of vision and ocular surface findings. The studies trend toward a lower rejection rate and graft failure with lr-CLAL. However, the level and duration of immunosuppression vary widely between the studies and may impact allograft rejections and long-term graft survival. Complications related to immunosuppression are minimal. Repeat surgery may be needed to maintain a viable ocular surface. Reasonable long-term success can be achieved with both KLAL and lr-CLAL with appropriate systemic immunosuppression. Proprietary or commercial disclosure may be found after the references.

Predictors of 24-month onset of macular fibrosis in type 3 macular neovascularisation

AimsTo explore prognostic multimarker models for progression to macular fibrosis (MF) over 24 months specific to type 3 macular neovascularisation (T3 MNV).MethodsThis retrospective, exploratory, single-centre, cohort study comprised 65 eyes...

An Updated Analysis of Ocular Adverse Events and Vision-Related Functioning in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Belantamab Mafodotin, Lenalidomide, and Dexamethasone in the Phase 1/2 Belard Trial

Introduction Belantamab mafodotin (belamaf; GSK2857916) is a B-cell maturation antigen-binding antibody-drug conjugate approved as a monotherapy in pretreated patients (pts) with relapsed/refractory multiple myeloma. Ocular adverse events (OAEs), manifesting as visual acuity changes, ocular symptoms, and corneal findings, are common with belamaf and the main reason for dose modifications (dose reduction, dose holds) or treatment discontinuation. In this descriptive analysis, we evaluate the OAEs and their impact on daily functioning in transplant ineligible (TI) pts with newly diagnosed multiple myeloma (NDMM), treated with an extended dosing schedule of belamaf in combination with lenalidomide and dexamethasone (Rd) in the phase 1/2 BelaRd study. Methods BelaRd (NCT04808037) is an open-label, phase 1/2 study conducted in Greece, aiming to enroll 66 TI NDMM pts. The study is comprised of 2 Parts: Part 1 evaluates the safety/clinical activity of three different belamaf doses (2.5/1.9/1.4 mg/kg) plus Rd and establishes the recommended phase 2 dose (RP2D). Part 2 further investigates the safety/efficacy of RP2D in two Groups and evaluates two different sets of guidelines for the management of OAEs. In Part 1, belamaf is initially administered q8w and, depending on toxicity, dosing may be adjusted to q12w. Ocular assessments include best corrected visual acuity (BCVA), using Snellen chart and manifest refraction, and corneal exam using slit lamp microscopy. Ocular symptoms are classified by Common Terminology Criteria for Adverse Events v5.0, while dry eye disease severity and vision-related functioning is assessed with the patient-reported questionnaire Ocular Surface Disease Index (OSDI). In Part 1 of the study, severity of corneal events is assessed with the Keratopathy Visual Acuity scale. This descriptive analysis presents the OAEs in all Part 1 pts over an extensive follow-up period (data cut-off: 05 June 2023). Results Thirty-six pts were included in this analysis, who were followed up for a median of 20.3 months (range 3.2-26.8). At baseline, all pts had ocular comorbidities. Among 216/244/201 BCVA assessments in cohorts 2.5/1.9/1.4 mg/kg, a meaningful BCVA decline (BCVA <20/50) with at least 3 lines drop in the better seeing eye, was observed in 21 (10%)/24 (10%)/17 (8%) of the assessments, while BCVA ≤20/200 with at least 3 lines drop in the better seeing eye was noted in only 2 (1%)/3 (1%)/8 (4%), with a median time to resolution of 1 month. The most frequently reported ≥Gr 3 ocular symptom was decreased vision, observed in 11 (5%)/ 8 (3%)/ 7 (3%) of the assessments, while ≥Gr3 keratopathy was noted in < 2% of assessments across all cohorts. Regarding OSDI, from 202/234/196 responses received, the number of “all/most” of the time worst responses in the ocular symptoms category were 6 (3%)/6 (3%)/8 (4%), while the respective proportions in the Activities of Daily Living category (ADL) were 6 (3%)/4 (2%)/3 (2%). In terms of missed doses due to OAEs, among 129/138/119 planned belamaf infusions, the number of skipped doses were 53 (41%)/48 (35%)/32 (27%). The overall response rate was 100%, no disease progression was observed over a median follow-up of 20.3 months, and 30 (83%) patients achieved at least VGPR while 19 (53%) achieved at least CR, with a median time to first response of 1 month. Conclusions Over a prolonged follow-up period, the belamaf-Rd triplet, with the extended dosing schedule for belamaf, had a minimal impact in vision-related functioning, as the ‘all/most’ of the time worst answers in the ADL category of OSDI was ≤3% across all cohorts. Furthermore, the frequency of clinically relevant impairment in vision was low, as a meaningful BCVA decline was observed in <10% of assessments, with a rapid time to resolution. Finally, the treatment combination induced rapid, deep and durable responses across all dose levels, with no PD observed. In conclusion, this novel extended belamaf schedule nearly eradicates the risk for clinically relevant ocular toxicity and impact on ADL, without any compromise in clinical activity, suggesting it may be a valid option in the upfront treatment of this frail, elderly and difficult-to-treat pt population.

Evaluation of a Novel Method for the Assessment of Ocular Adverse Events and Associated Functional Impact in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Belantamab Mafodotin, Lenalidomide, and Dexamethasone in the Phase 1/2 Belard Trial

Introduction Belantamab mafodotin (belamaf; GSK2857916), an antibody-drug conjugate targeting B-cell maturation antigen, has shown promising efficacy and a favorable tolerability profile in the treatment of multiple myeloma. Ocular adverse events (OAEs), manifesting as visual acuity changes, ocular symptoms, and corneal findings, are common with belamaf and the main reason for dose modifications (dose reduction, dose holds) or treatment discontinuation. Keratopathy and Visual Acuity (KVA) scale was used in most belamaf trials, including the pivotal DREAMM-2, to guide belamaf dose modifications. KVA grading is dependent on an ophthalmologist consultation prior to belamaf administration. Herein, we evaluate a novel approach to guide belamaf dosing in transplant ineligible (TI) patients (pts) with newly diagnosed multiple myeloma (NDMM), treated with an extended dosing schedule of belamaf in combination with lenalidomide and dexamethasone (Rd) in the phase 1/2 BelaRd study. Methods BelaRd (NCT04808037) is an open-label, phase 1/2 study conducted in Greece, aiming to enroll 66 TI NDMM pts. Part 1 evaluated the safety/tolerability of three belamaf doses (2.5/1.9/1.4 mg/kg) plus Rd in 36 pts and established that the recommended phase 2 dose (RP2D) is 1.9 mg/kg, initially administered q8w and, depending on toxicity, adjusted to q12w. Part 2 investigates the safety/efficacy of RP2D in Groups A and B, comprised of 15 pts each, and evaluates two different sets of guidelines for the management of OAEs. In Group A, belamaf dosing is guided by the KVA scale; in Group B, dose modifications are determined by the pts' responses on ocular symptoms and their impact on activities of daily living (ADL), captured by the Vision Related Anamnestic (VRA) tool, and by the presence of ≥Grade (Gr) 3 KVA events (BCVA reduced/corneal findings). VRA is a novel, 9-item physician administered questionnaire designed to assess the frequency of ocular symptoms and their impact on vision-related activities. Ocular exams include Snellen best corrected visual acuity (BCVA) and slit lamp corneal evaluation, while ocular symptoms are classified by CTCAE v5.0. Herein, we present the OAEs and the clinical activity of the treatment combination for both Groups of Part 2 (cut-off date 05/06/2023). Results By the cut-off date, twenty-four pts [median age: 75.5 years; male: 16 (66.7%)] had received ≥ 1 belamaf dose in Part 2 and were still on treatment. At baseline, most pts had ocular comorbidities. The median belamaf administrations and number of cycles reached were 3.0/2.0 and 6.5/5.5, for Groups A and B, respectively. A meaningful BCVA decline (BCVA <20/50) with at least 3 lines drop in the better seeing eye, was noted in 5/52 (9.6%) and 5/45 (11.1%) assessments, while BCVA ≤20/200 with at least 3 lines drop was noted in 1/59 (1.7%) and 2/51 (3.9%), respectively. Overall, no ≥Gr 3 ocular symptoms were observed, while the most frequent ≥Gr 2 ocular symptom was dry eye (57/110, 51.8%); also, no ≥Gr3 keratopathies were recorded. Among 66/59 VRA assessments, ocular symptoms and ADL impairment, manifesting for >50% of the time (substantial time) in the last 24 hours prior to belamaf administration, were noted in 2 (3.0%)/9 (15.3%) and 2 (3.0%)/7 (11.9%), respectively. Importantly, numerically similar proportions of KVA events and skipped belamaf doses were noted in both Groups (Table 1). Furthermore, although the sample size of the present analysis does not allow conclusions for the VRA test characteristics, it is notable that in all assessments where eyesight difficulties were reported for substantial time, ≥Gr2 KVA events were also recorded, suggesting a potential association between VRA responses and KVA events, that warrants further investigation. Finally, in terms of clinical activity, for the 19 response-evaluable pts (≥2 efficacy assessments), at a median follow-up of 7.4 months the ORR was 90%/100% in Groups A and B (PR/VGPR: 30%/60%; 66.7%/33.3%) with no disease progression observed. Conclusions In this preliminary descriptive analysis, the VRA tool was safe and effective in informing belamaf dose adjustments in the extended dosing schedule. Recruitment in Part 2 is ongoing and, as data accumulates, future analyses will provide further insight on the potential association of the VRA tool with KVA events, which may eliminate the need for an ophthalmic exam prior to belamaf dosing.

Long-Term Safety and Efficacy Results of Belantamab Mafodotin Plus Lenalidomide and Dexamethasone in Transplant Ineligible Patients with Newly Diagnosed Multiple Myeloma: An Updated Part 1 Analysis from the Phase 1/2 Belard Trial

Introduction The preferred upfront treatment of transplant ineligible (TI) patients (pts) with newly diagnosed multiple myeloma (NDMM) consists of the combination of lenalidomide and dexamethasone (Rd) with a third antimyeloma agent of a different mechanism of action (e.g., proteasome inhibitors or anti-CD38 monoclonal antibodies). Belantamab mafodotin (belamaf; GSK2857916), an antibody-drug conjugate targeting BCMA, has shown efficacy in pretreated MM pts, while preclinical data demonstrate synergy between belamaf and lenalidomide, with no overlapping toxicities. Thus, there is a strong rationale for investigating the belamaf-Rd triplet in TI NDMM pts. Methods BelaRd (NCT04808037) is an open-label, phase 1/2 study conducted in Greece, aiming to enroll 66 TI NDMM pts. Eligible are adult pts with ECOG PS 0-2 and adequate organ function. Part 1 evaluates the safety/tolerability of three belamaf doses (2.5/1.9/1.4 mg/kg) plus Rd in 36 pts and establishes the recommended phase 2 dose (RP2D). In this part, belamaf is initially administered q8w and, depending on toxicity, dosing may be adjusted to q12w. Ocular exams include Snellen best corrected visual acuity (BCVA) and slit lamp corneal evaluation. Ocular symptoms are classified by CTCAE v5.0, while the Ocular Surface Disease Index (OSDI) captures dry eye disease and activities of daily living (ADL).Herein, we present updated safety and efficacy results of all Part 1 pts with an extended follow-up time (cut-off date 05/06/2023). Results Of the 36 pts [median age: 72.5 years; male: 19 (53%)] in Part 1, 29 (81%) are still on treatment, while 7 (19%) have discontinued [6 pts due to belamaf-unrelated fatal events: (COVID-19: 1/1/2; Pneumonia: 1/1/0, for cohorts 2.5/1.9/1.4 respectively); 1 pt withdrew consent]. The median belamaf administrations and number of cycles reached were 6/7/7 and 20.0/22.5/20.0, for the respective cohorts. The most common (≥10% of pts) non-ocular ≥ Gr3 treatment-emergent adverse events were fatigue (21 pts, 58%; [7 (58%)/7 (58%)/7 (58%)]), diarrhoea (8 pts, 22%; 2 (17%)/3 (25%)/3 (25%)]), rash (6 pts, 17%; [2 (17%)/2 (17%)/2 (17%)]), COVID-19 (5 pts, 14%; [2 (17%)/1 (8%)/2 (17%)]) and insomnia (4 pts, 11%; 0/4 (33%)/0]) , while no ≥Gr3 thrombocytopenias and infusion-related reactions were reported. Regarding ≥Gr3 infections other than COVID-19, pneumonia was reported for 3 (8%) pts [1/1/1 (8%)] and lower respiratory tract infection for 1 (3%) pt [0/0/1(8%)]. Regarding ocular adverse events (OAEs), among 216/244/201 BCVA assessments in cohorts 2.5/1.9/1.4, a meaningful BCVA decline (BCVA <20/50) with at least 3 lines drop in the better seeing eye, was observed in 21 (10%)/24 (10%)/17 (8%), while BCVA ≤20/200 with at least 3 lines drop in the better seeing eye was noted in only 2 (1%)/3 (1%)/8 (4%), with a median time to resolution of 1 month. Across all cohorts, the most frequently reported ≥Gr 3 ocular symptom was decreased vision (26/665, 4%), while ≥Gr3 keratopathy was noted in <2% of assessments. Regarding OSDI, from 202/234/196 responses received, the number of “all/most” of the time worst responses in the ocular symptoms category were 6 (3%)/6 (3%)/8 (4%), while the respective proportions in the ADL category were 6 (3%)/4 (2%)/3 (2%). The overall response rate was 100% across all cohorts: More specifically CR or better was achieved by 7 (58%)/6 (50%)/6 (50%), VGPR by 3 (25%)/5 (42%)/3 (25%) and PR by 2 (17%)/1 (8%)/3 (25%) pts in cohorts 2.5/1.9/1.4, with a median time to first response of 1 month. Finally, at a median follow-up of 20.3 months, no disease progression was observed, median PFS and median time to progression were not reached ( Figure 1) and responses continue to deepen across all cohorts. Conclusions Over an extended follow-up period, the belamaf-Rd triplet has proven a safe and effective combination for the upfront treatment of TI NDMM pts, with no long-term safety signals. Furthermore, the extended dosing schedule for belamaf had a minimal impact in vision-related functioning, as very low rates of meaningful BCVA decline and “most/all” OSDI responses were noted across all cohorts, with a rapid time to resolution. Meanwhile, a very promising clinical activity is observed, with rapid, deep and durable responses across all dose levels. Consequently, after validation with bigger pt numbers, this novel combination may well be a very attractive frontline option for this vulnerable and difficult-to-treat pt population.

Predictive potential of optical coherence tomography parameters for the prognosis of decreased visual acuity after trabeculectomy in open-angle glaucoma patients with good vision

BackgroundTrabeculectomy (trab) is the most effective surgical procedure for lowering IOP and preventing glaucoma progression. However, decline in best-corrected visual acuity (BCVA) is one of the most serious postoperative complications of trab. Here, we investigated methods to predict decreased BCVA after trab in glaucoma patients with good preoperative BCVA.MethodsThis study included 35 eyes of 35 open-angle glaucoma (OAG) patients (male / female: 21 / 14, age: 64.0 ± 9.7 years old, preoperative intraocular pressure: 15.9 ± 5.4 mmHg, mean deviation: -18.1 ± 5.6 dB) with preoperative BCVA of 0.7 or better who underwent trab and were observed for more than 12 months. As a preoperative analysis, we measured temporal quadrant circumpapillary retinal nerve fiber layer thickness (cpRNFLT) and ganglion cell complex thickness in a central strip between the disc and fovea (csGCCT), an area that corresponds to the location of the papillomacular bundle (PMB) in swept-source optical coherence tomography (OCT). We defined BCVA decline as a loss of more than 3 lines of BCVA after 12 months. Measurement parameters were compared between the BCVA-decline group and the non-BCVA-decline group.ResultsBCVA decline was detected in 11 cases (31.4%) 12 months after trab. There was a statistically significant difference in axial length (P = 0.049). A single logistic analysis showed that the BCVA-decline group had significantly lower cpRNFLT than the non-BCVA-decline group (27.7 ± 8.0 μm vs. 45.1 ± 5.3 μm, P < 0.001, cut-off value: 33.4 μm), as well as lower csGCCT (72.4 ± 7.7 μm vs. 87.5 ± 5.1 μm, P = 0.002, cut-off value: 82.3 μm). Multivariable logistic analysis showed that the BCVA-decline group had significantly lower temporal quadrant cpRNFLT (P < 0.001) and lower middle csGCCT (P < 0.001) compared to the non-BCVA-decline group.ConclusionsLower temporal quadrant cpRNFLT and middle csGCCT, OCT scan areas that correspond to the location of the PMB, might be biomarkers that predict BCVA decline after trab in OAG patients with good vision.

Incidence of wound dehiscence after keratoplasty: a meta-analysis of observational studies.

The comprehensive investigation of the association between keratoplasty and wound dehiscence remains limited, despite corneal disease being a leading cause of visual impairment. A meticulous search strategy was executed across prominent databases such as Web of Science, PubMed, Cochrane Library, and Embase. Data relevant to our research objective were extracted from eligible studies. The methodological quality of each study was assessed using the ROBINS-I tool, while statistical analysis was conducted utilizing STATA 17.0. To evaluate potential publication bias, the Funnel plot and Egger's test were employed. A total of 11 articles were deemed suitable for inclusion in our analysis. Our findings indicate that the overall incidence of wound dehiscence following keratoplasty was estimated to be 1.9% (95% CI: 0.013, 0.026), although substantial heterogeneity was observed (I2 = 72.798%). Notably, developed countries exhibited a higher incidence of wound dehiscence compared to their developing counterparts. Furthermore, the occurrence of wound dehiscence was found to be lower in deep anterior lamellar keratoplasty (DALK) procedures when compared to penetrating keratoplasty (PK). Analysis utilizing Egger's linear regression method yielded no evidence of publication bias (p = 0.91). Moreover, within the first year post-keratoplasty, approximately 31.4% of patients experienced wound dehiscence (95% CI: 0.149, 0.503), and 43.1% exhibited a decline in best-corrected visual acuity (BCVA) (95% CI, 0.341, 0.522). The results of our study unveiled the occurrence rate of wound dehiscence following keratoplasty, exhibiting variations based on economic level and the specific surgical procedure employed. Furthermore, onset time of wound dehiscence and visual acuity warrant consideration.

Clinical and genetic characterization of a large cohort of Chinese patients with Bietti crystalline retinopathy.

To investigate the clinical and genetic characteristics for a large cohort of Chinese patients with Bietti crystalline retinopathy (BCR). A total of 208 Chinese BCR patients from 175 families were recruited. Comprehensive clinical evaluations and genetic analysis were performed. Genotype-phenotype correlations were evaluated through statistical analysis. The patients' median age was 37 years (range, 20-76 years). The median best corrected visual acuity (BCVA) was 0.8 LogMAR unit (range, 2.8 to -0.12). A significant decline of BCVA was revealed in patients over 40 years old (P<0.001). Two clinical types were observed: peripheral type (type P) and central type (type C). Significantly more type C patients had a worse central visual acuity, but a more preserved retinal function (P<0.05). Molecular screening detected biallelic CYP4V2 pathogenic variants in 98.3% (172/175) of the families, including 19 novel ones. The most frequent pathogenic variant was c.802-8_810del17insGC, with the allele frequency of 55.7% (195/350), followed by c.992A>C (28/350, 8%) and c.1091-2A>G (23/350, 6.6%). BCR patients with one c.802-8_810del17insGC and one truncating variant (IVS6-8/Tru) had BCVA>1.3 LogMAR unit (Snellen equivalent<20/400) at a younger age than those with homozygous c.802-8_810del17insGC variants (homo IVS6-8) (P=0.031). BCR patients preserved relatively good vision before 40 years old. Two distinct clinical types of BCR were observed. BCR patients with IVS6-8/Tru had an earlier decline in visual acuity than those with homo IVS6-8. Our findings enhance the knowledge of BCR and will be helpful in patient selection for gene therapy.

Factors Associated With Visual Acuity Decline in Glaucoma Patients With Loss of Ganglion Cell Complex Thickness.

To investigate the association between ocular/systemic factors and visual acuity decline in glaucoma patients with loss of ganglion cell complex thickness (GCCT). In 515 eyes of 515 patients with open-angle glaucoma (mean age, 62.6 ± 12.8 years; mean deviation, -10.95 ± 9.07 dB), we used swept-source optical coherence tomography to measure macular GCCT in sectors classified as corresponding to circumpapillary retinal nerve fiber layer clock-hour sectors from 7 o'clock (inferotemporal) to 11 o'clock (superotemporal). We calculated Spearman's rank correlation coefficient between each sector and best-corrected visual acuity (BCVA), determined cutoff values for BCVA decline (<20/25), and used multivariable linear regression models to determine the correlation between BCVA and biological antioxidant potential (BAP), corneal hysteresis (CH), and temporal-tissue optic nerve head blood flow (represented by temporal mean blur rate, or MBR-T). Macular GCCT corresponding to the 9 o'clock sector had the highest correlation with BCVA (Rs = -0.454; P < 0.001) and a cutoff of 76.17 µm (area under the receiver operating characteristic curve = 0.891; P < 0.001). Subjects below this cutoff (N = 173) showed significant correlations between BCVA and age, BAP, CH, and MBR-T (β = 0.192, P = 0.033; β = -0.186, P = 0.028; β = -0.217, P = 0.011; and β = -0.222, P = 0.010, respectively). Multiple factors are involved in BCVA decline in patients with glaucoma with decreased macular GCCT. This suggests that evaluating BCVA may require assessing multiple factors. Multiple factors contribute to BCVA decline.

Ocular adverse events in transplant ineligible patients with newly diagnosed multiple myeloma treated with belantamab mafodotin plus lenalidomide/dexamethasone from the phase 1/2 BelaRd study.

e20031 Background: We report the belantamab mafodotin (belamaf)-associated ocular adverse events (OAEs) in transplant ineligible (TI) patients (pts) with newly diagnosed multiple myeloma (NDMM) treated with belamaf plus lenalidomide and dexamethasone (Rd). Methods: BelaRd (NCT04808037), an ongoing, prospective, open-label, phase 1/2 study, aims to enroll 66 TI pts with NDMM. In Part 1, assessing the safety/clinical activity of belamaf plus Rd, 36 pts are randomized (1:1:1) to receive belamaf 1.4, 1.9, or 2.5 mg/kg doses Q8W. Eye exams include Snellen best corrected visual acuity (BCVA) and corneal exam. Ocular symptoms are graded by CTCAE v5.0, and dry eye disease severity/activities of daily living (ADLs) are assessed with the Ocular Surface Disease Index (OSDI). This descriptive analysis included all Part 1 pts (cutoff: 15/12/2022). Results: Pts (N = 36) were followed up for a median 15 months. At baseline all pts had ocular comorbidities. Regarding pts visual acuity, out of a total of 499 BCVA assessments, 164 (33%) were Gr 2 [1.4, 1.9, 2.5 mg/Kg: 46/157 (29%), 49/182 (27%), 69/160 (43%)] and 54 (11%) were Gr 3 [1.4, 1.9, 2.5 mg/Kg: 18/157 (11%), 16/182 (9%), 20/160 (13%)]. Notably, a meaningful BCVA decline (worse than 20/50 in better seeing eye) was observed in 38 (8%) assessments [1.4, 1.9, 2.5 mg/Kg: 12/151 (8%), 13/182 (7%), 13/160 (8%)], with a median time to resolution of 1 month. Regarding clinically relevant Gr ≥2 ocular symptoms, blurred vision, dry eye and visual impairment were observed in 38 (8%), 96 (20%) and 98 (20%) assessments, with a median time to resolution of 2, 3 and 2 months, respectively. Slit lamp examinations by the ophthalmologist (N = 501) revealed a Gr 2 keratopathy in 55 (11%) assessments [1.4, 1.9, 2.5 mg/Kg: 17/158 (11%), 18/183 (10%), 20/160 (13%)] and Gr 4 keratopathy in 2 ( &lt; 1%) assessments [1.4, 2.5 mg/Kg: 1/158 ( &lt; 1%), 1/160 (1%)], with a median time to resolution of 4 months. The proportion of belamaf doses withheld /planned due to OAEs was 26% (24/94), 26% (28/106) and 36% (35/98) in the 1.4, 1.9 and 2.5 mg/Kg cohorts. Regarding OSDI findings, in the ocular symptoms category (Q1–5), the proportions of assessments with ‘all’ or ‘most’ of the time worst answers were 0%, 1% (1/173), 0% and 6% (8/146), 2% (4/173), 3% (5/146), in the 1.4, 1.9, 2.5 mg/Kg cohorts, respectively. The proportions of assessments with ‘all’ or ‘most’ of the time worst answers to ADLs (Q6–9) were 1% (1/146), 0%, 1% (1/146) and 1% (2/146), 2% (3/173), 3% (5/146) in the 1.4, 1.9, 2.5 mg/Kg cohorts. Conclusions: No new ocular safety signals were observed with belamaf plus Rd in the upfront treatment of TI pts with NDMM. A meaningful BCVA decline was observed in a minority ( &lt; 10%) of assessments which resolved quickly (1 month). Most importantly, a minor impact on daily functioning, ‘all’ or ‘most’ of the time, was noted with the combination. Clinical trial information: NCT04808037 .

Safety and clinical activity of belantamab mafodotin plus lenalidomide and dexamethasone in transplant ineligible patients with newly diagnosed multiple myeloma: The phase 1/2, prospective, open-label, BelaRd study.

8050 Background: We present the updated safety and efficacy of upfront belantamab mafodotin (belamaf) plus lenalidomide and dexamethasone (Rd) in transplant ineligible (TI) pts with newly diagnosed multiple myeloma (NDMM). Methods: The ongoing, prospective, open-label, phase 1/2 BelaRd study (NCT04808037) aims to enroll 66 pts with TI NDMM, with ECOG PS &lt; 2 and adequate organ function. In Part 1, 36 pts are randomized (1:1:1) to receive belamaf 2.5, 1.9, or 1.4 mg/kg Q8W plus Rd. Eye exams include Snellen best corrected visual acuity (BCVA) and corneal exam (slit lamp examination). Ocular adverse evets (OAEs) are classified by CTCAE v5.0. This descriptive analysis presents the updated safety and efficacy findings for all Part 1 pts (cutoff date 15/12/22). Results: The analysis included 36 pts [median age: 73 years (64–86); male: 19 (53%)], of whom 31 (86%) were still on treatment and 5 (14%) had discontinued [4 pts due to belamaf-unrelated adverse events (AEs); 1 pt withdrew consent]. At baseline, 32 (89%) pts were intermediate fit as per International Myeloma Working Group frailty score and 34 (94%) had ECOG PS≤1. Median follow up was 15 months (3–23); median belamaf administrations and number of cycles reached were 6 (2–10) and 15 (3–22). Thirty-four (94%) pts experienced ≥1 grade (Gr) ≥3 treatment-emergent AEs (TEAEs). Most common (≥ 10% of pts) non ocular Gr ≥3 TEAEs were fatigue (21 pts, 58%), rash (6 pts, 17%), diarrhoea (5 pts, 14%) and COVID-19 infection (4 pts, 11%); no Gr ≥3 thrombocytopenias and any Gr infusion-related reactions were reported. Regarding pts visual acuity, out of a total of 499 BCVA assessments, 164 (33%) were Gr 2 and 54 (11%) were Gr 3. Notably, a meaningful BCVA decline (worse than 20/50 in better seeing eye) was observed in 38 (8%) assessments, with a median time to resolution of 1 month. Regarding clinically relevant Gr≥2 ocular symptoms, blurred vision, dry eye and visual impairment were observed in 38 (8%), 96 (20%) and 98 (20%) assessments, with a median time to resolution of 2, 3 and 2 months. Slit lamp examinations by the ophthalmologist (N = 501) revealed a Gr 2 keratopathy in 55 (11%) assessments and Gr 4 keratopathy in 2 ( &lt; 1%) assessments, with a median time to resolution of 4 months. Overall response rate [partial response (PR) or better] was 100.0% [36 pts; stringent complete response: 14% (5 pts); complete response: 19% (7 pts); very good partial response: 47% (17 pts); PR: 19% (7 pts)]. Median time to first response was 1 month. Conclusions: Part 1 of the BelaRd study showed that in TI pts with NDMM, the safety profile of belamaf plus Rd was manageable and a meaningful BCVA decline was noted in a minority ( &lt; 10%) of assessments which resolved quickly (1 month). The combination induced rapid and deep responses, with all pts achieving ≥PR and first response observed at a median of 1 month. Clinical trial information: NCT04808037 .

Unexplained visual loss after primary pars-plana-vitrectomy with silicone oil tamponade in fovea-sparing retinal detachment

BackgroundTo investigate the incidence and clinical characteristics of unexplained visual loss in patients with fovea-sparing rhegmatogenous retinal detachment (RRD) during or after silicone oil (SO) tamponade.MethodsThe medical charts of all patients with macula-on RRDs, who underwent pars-plana-vitrectomy (ppV) with SO tamponade were retrospectively assessed regarding unexplained visual loss (UVL) of ≥ 3 Snellen lines and alterations on optical coherence tomography (OCT) during or after SO tamponade. The clinical data analysed included visual acuity, surgical parameters, OCT images, duration of SO tamponade and the time point of visual decline. Cases with re-detachment or secondary causes of visual loss such as SO emulsification, epiretinal membranes or macular edema were excluded.ResultsOver a 15-year-period, 22 cases with macula-on RRD, which had primarily been treated with ppV and SO tamponade, met the inclusion criteria. In most eyes (n = 20; 91%), the RRD was caused by a giant retinal tear (GRT). In 11 of these 22 cases (50%), best-corrected visual acuity (BCVA) had dropped by at least 3 lines for no apparent reason. In these 11 cases, mean preoperative logMAR BCVA was 0.2 (SD 0.13; range 0-0.5), equal to Snellen’s VA of 0.63, and mean postoperative logMAR BCVA 1.0 (SD 0.24; range 0.5–1.3), equal to Snellen’s VA of 0.10. Visual decline occurred about 12 weeks postoperatively (SD 6.2; range 3–20 ) and comprised 8 lines (SD 2.3; range -11 to -4). SO was removed on average 139 (SD 50.0; range 88–271) days after the first ppV. In 9 cases visual decline occurred while the SO was in-situ. In 2 patients, BCVA decline was noted 2 weeks after SO removal. In all eyes, preoperative central foveal thickness (CFT) was 254 μm (SD 24.2), which decreased to 224 μm (SD 29.6) during SO tamponade and increased to 247 μm (SD 29.2) after SO removal, irrespective of the presence of UVL. The mean follow-up time was 20 months (SD 30.6) after SO removal.ConclusionUVL after SO tamponade for macula-on RRD is more frequent than expected. The incidence in our case series was 50%. The mechanism of this phenomenon is still unknown. In general, vitreoretinal surgeons should thoroughly question the need for SO tamponade, inform their patients of possible UVL and remove SO as early as possible.Trial registrationThe study was approved by the local ethics committee on 6th of May 2022 (Ethikkommission der Universität Regensburg, Votum 22-2925-104) and was conducted in accordance with the ethical standards of the Declaration of Helsinki.

Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma, a Real-World Single Center Experience

Introduction Belantamab mafodotin is an antibody drug conjugate targeting B-cell maturation antigen (BCMA) with single agent activity around 32% in the DREAMM2 phase II trial (Lonial et al, Cancer 2021). Side effects, including keratopathy and reduced best corrected visual acuity (BCVA), often necessitate dose reduction and dose delays which may limit efficacy. The aim of this study was to assess response rates, dose modifications, and frequency of ocular adverse events in patients treated with belantamab mafodotin in a real-world setting and in relation to prior treatment with BCMA targeted therapies. Methods All patients treated with at least one dose of commercial belantamab mafodotin at Memorial Sloan Kettering Cancer Center between October 1, 2020 and July 11, 2022 were included in the study. Descriptive statistics were used to assess patient characteristics, response rates, and rate of adverse events. Kaplan Meier curves were used to assess progression free survival (PFS) and overall survival (OS). Results Eighty-two relapsed/refractory multiple myeloma patients were included; 40 (49%) were women median age was 68 years, and 50 patients (61%) had high risk cytogenetics. Twelve patients were treated on the Expanded Access Program with belantamab mafodotin prior to receiving commercial drug. Patients had a median of 6 (range 2-14) prior lines of therapy, all had received an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody. Sixteen patients (20%) had received one or more BCMA-targeted agents including a bi-specific antibody (N=5), chimeric antigen receptor (CAR) T cell (N=12), and trial therapy with belantamab mafodotin (N=1). Patients received a median of 4 cycles (range 1-31) of belantamab mafodotin. The majority, 96% (N=79), as single agent, while 3 patients were received belantamab mafodotin in combination with other anti-myeloma agents. The overall response rate (ORR) in all patients was 45%; 37/82 patients. Of these, 10 achieved a partial response (PR); 14 patients achieved a very good partial response (VGPR), and 13 patients achieved a complete response (CR) (Table). The median duration of response for patients in the ORR cohort was 11 months. Eighteen patients had stable disease (SD) and 27 patients had progressive disease (PD). The median PFS was 6 months and median OS was not reached. At the end of follow up, 19 patients continued belantamab mafodotin therapy and 28 patients had died. In a separate analysis of patients not included in the Expanded Access Program, the ORR was 43%; 8 had a PR, 13 had a VGPR, and 8 patients had a CR. Of the 16 patients who had prior exposure to BCMA targeted therapy, 5 patients had a PR or better (3 VGPR, 2 CR), 2 patients were in a VGPR/CR at start and continued to respond, 3 patients had SD while 6 patients had PD. The median PFS was similar in patients that were BCMA exposed and those that were BCMA naïve (Figure). Fifty-six patients (68%) had any grade of ocular toxicity per the Keratopathy and Visual Acuity (KVA) scale; 26 patients had grade 1, 15 grade 2, 12 grade 3, and 2 patients had grade 4 keratopathy, respectively. Twenty-six patients had presence of corneal microcysts (information missing in 11 patients). Forty-five patients experienced a decline in BCVA; 22 patients had grade 1, 13 had grade 2, 3 had grade 3, and 1 patient had grade 4 decline in BCVA, respectively (grade missing in 4 patients). The dose of belantamab mafodotin was reduced from 2.5 mg/kg to 1.92 mg/kg in 36 patients while 29 patients had dose delays, the majority due to ocular adverse events but also due to baseline cytopenia, infection, and patient preference. Most patients who had dose modifications due to ocular events were able to continue therapy on a lower dose with maintained response. Nine patients discontinued treatment due to keratopathy, 3 of whom had ongoing grade 1 keratopathy at the end of follow up. Conclusion In this heavily pre-treated multiple myeloma patient population, the ORR was 43-45% which is similar or better than the DREAMM2 phase II trial. The rate of ocular toxicity (68% keratopathy) was comparable to previous reports. Importantly, 5 of 16 patients with exposure to prior BCMA exposure achieved a PR or better while 5 had SD. The PFS was similar in BCMA exposed and BCMA naïve patients. These are encouraging outcomes for belantamab mafodotin in the real-world setting with responses and toxicities comparable to those reported in clinical trials. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Single-Agent Belantamab Mafodotin in Patients with Relapsed or Refractory Multiple Myeloma: Final Analysis of the DREAMM-2 Trial

Introduction: Belantamab mafodotin (belamaf) is a first-in-class, B-cell maturation antigen-binding antibody-drug conjugate containing monomethyl auristatin F. Belamaf eliminates myeloma cells by a multimodal mechanism: direct cell kill and anti-myeloma immune response. In the primary1 and 13-month follow-up2 DREAMM-2 study analyses in patients with RRMM, belamaf monotherapy demonstrated deep and durable responses, with a manageable safety profile. The aim of this report is to analyze the efficacy/safety profile of belamaf using final data from the pivotal DREAMM-2 study. Methods: DREAMM-2 (NCT03525678) is a Phase 2, 2-arm, open-label study of single-agent belamaf in patients with triple-refractory RRMM who had ≥3 prior therapies and were refractory to an immunomodulatory agent, and a proteasome inhibitor, and refractory or intolerant to an anti-CD38 mAb. Belamaf doses evaluated were 2.5 and 3.4 mg/kg every 3 weeks (Q3W). The primary endpoint was overall response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS), safety, ocular symptoms, and health-related quality of life. Eye exams, including a corneal exam and assessment of change in best corrected visual acuity (BCVA), were conducted at baseline and prior to each dose. The GSK Keratopathy and Visual Acuity scale was used for grading ocular events. Recovery was defined as Grade 1 exam findings/no exam findings, and ≤1-line decline in BCVA vs baseline. Ocular symptoms were graded per CTCAE version 4.03. Patients completed patient-reported outcomes questionnaires during treatment at baseline and Q3/6W. Results: At the cutoff date (31Mar22), the median duration of follow-up for patients randomized to the belamaf 2.5 mg/kg cohort (N=97) was 12.48 months (range 0.1-40.4), and 13.77 (0.1-42.8) months for patients randomized to the 3.4 mg/kg cohort (N=99) (Table). The ORR in the 2.5 mg/kg and 3.4 mg/kg groups was 32% and 35%, respectively; 19% and 24% of patients (58% and 69% of responders) achieved very good partial response (VGPR) or better. Median time to response was 1.5 months (95% CI 1.0, 2.1) in the 2.5 mg/kg cohort and 1.4 months (0.9, 2.1) in the 3.4 mg/kg cohort. The MRD negativity rate of patients with ≥VGPR was 36% and 23% for the 2.5 and 3.4 mg/kg cohorts. Median duration of response was 12.5 and 6.2 months for the 2.5 and 3.4 mg/kg cohorts. Median PFS was 2.8 and 3.9 months. Median Kaplan-Meier estimated OS was 15.3 and 14.0 months. In patients who achieved ≥VGPR, median PFS was 14.0 and 16.8 months for the 2.5 and 3.4 mg/kg cohorts, respectively. In patients who achieved ≥VGPR, estimated OS was 30.7 and 35.5 months. The 3 most common Grade ≥3 adverse events (AEs) were keratopathy, anemia, and thrombocytopenia (Table). AE-related dose reductions occurred in 36% and 44%, dose delays occurred in 54% and 62%, and AE-related permanent discontinuations occurred in 9% and 5% for the 2.5 and 3.4 mg/kg cohorts, respectively; discontinuation due to ocular events was rare (3% in both cohorts). The most commonly reported ocular events in the 2.5 mg/kg cohort included keratopathy (71%), blurred vision (23%), BCVA reduced to 20/50 (21%), and dry eye (15%). BCVA changes and blurred vision were transient; up to 86% of all patients who had experienced blurred vision or worsening BCVA had resolution by the end of follow up. No permanent complete vision loss occurred. Despite changes in BCVA and blurred vision, EORTC-QLQ-C30 data suggest that overall Global Health Status/QoL, Physical and Role functioning, and overall disease symptoms were maintained or improved during treatment. Conclusions: This final analysis of DREAMM-2 confirms earlier reports1,2 that single-agent belamaf (2.5 mg/kg and 3.4 mg/kg) results in rapid, deep, durable, and clinically meaningful responses with a manageable safety profile in patients with RRMM. No new safety signals were observed. Dose modification remained effective in resolving ocular events and allowed patients the clinical benefit gained from continuing treatment with belamaf. Patient quality of life was maintained or improved despite changes in ocular symptoms. 1. Lonial S, et al. Lancet Oncol. 2020;21:207-21; 2. Lonial S, et al. Cancer. 2021;127:4198-212. Funding: GSK (Study 205678). Drug linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Iris abnormalities may influence the efficacy and filtration strategies of Posner-Schlossman syndrome: a retrospective study involving trabeculectomy, ExPRESS and Ahmed valve implants.

To evaluate and compare the one-year efficacy and influencing factors of different filtration surgeries on Posner-Schlossman syndrome (PSS) patients. A retrospective study enrolling 91 PSS patients who underwent filtering surgeries and were followed for at least one year. Unilateral PSS was diagnosed as recurrent attacks of mild, unilateral, non-granulomatous anterior uveitis, elevated intraocular pressure (IOP), keratic precipitates (KPs) on the corneal endothelium, open angle, no posterior synechia, and no inflammatory lesions in the posterior segment; the IOP and anterior segment returned to normal between attacks. Medical histories and thorough ocular examination results were collected. Trabeculectomy and ExPRESS were chosen as the first line and AGV was considered for those under high risk of fibrosis. Follow-up data, mainly IOP, best-corrected visual acuity (BCVA), and anterior segment manifestations at the 1st week, 6th month, and 12th month were generated and analyzed. Iris abnormalities were determined by depigmentation or atrophic changes on the anterior segment photograph. Complete surgical success was defined as 5 mmHg < IOP ≤ 21 mmHg without IOP-lowering drug or needle revision; qualified surgical success was defined as 5 mmHg < IOP ≤ 21 mmHg with IOP-lowering drugs or needle revisions. Survival analysis was performed to obtain the success rates. At the 12th month, the complete surgical success rate of trabeculectomy (N = 54), ExPRESS (N = 23), and AGV group (N = 14) was 58.97% (95%CI 46.91-77.09%), 84.21% (95%CI 68.33-100.87%), and 100%; the qualified success rate was 71.79% (95%CI 62.46-88.34%), 89.47% (95%CI 77.07-103.33%), and 100%, respectively. Patients undergoing trabeculectomy experienced the largest decline of BCVA (from 0.58±0.46 to 1.01±0.51, P < .05); the trabeculectomy group endured the highest IOP (20.84±9.92 mmHg) compared to ExPRESS (14.51±2.86 mmHg, P < .05) and AGV group (13.17±3.32 mmHg, P < .05). At the 12th month, in the ExPRESS group, patients with iris abnormalities had higher IOP than the normal ones (15.65±2.05 mmHg, 12.93±3.17 mmHg, P < .05). ExPRESS helped patients with iris abnormalities maintain lower IOP than trabeculectomy (15.65±2.05 mmHg, 22.52±10.67 mmHg, P < .05). Three patients developed hypotony at the 3rd month (1 in ExPRESS and 2 in trabeculectomy group). AGV and ExPRESS performed better than trabeculectomy in PSS patients in terms of IOP and success rate. Iris abnormalities might influence the postoperative IOP and this may be valuable in guiding filtration strategies. Chinese Clinical Trial Registry (No. ChiCTR1800017532, date: 2018/08/02).

Recurrent retinal detachment after pars plana vitrectomy with silicone oil tamponade for rhegmatogenous retinal detachment.

The recurrence of retinal detachment following rhegmatogenous retinal detachment (RRD) is a relatively common complication that can lead to reduced visual acuity and requires further surgery. The purpose of this study was to investigate the risk factors and visual outcomes of recurrent RRD following pars plana vitrectomy (PPV) with silicone oil tamponade for primary RRD. This was a retrospective follow-up study of 343 eyes that underwent initial PPV surgery with silicone oil tamponade for primary RRD. Patients were divided into a recurrence group and a reattachment group. The main outcome measures included causative factors, visual outcomes related to the recurrence of RRD, and the perioperative factors most affecting the recurrence of RRD. After retinal reattachment, we observed RRD recurrence after PPV for primary RRD in 42 out of 343 eyes (12.2%) during the follow-up period. Most causes of recurrence (69%) occurred within 6months of surgery. Multivariate logistic regression analysis showed that a PVR ≥ Grade C (odds ratio [OR]: 4.015; 95% confidence interval [CI] 1.721-9.367; P = 0.001) was a significant predictor for the development of recurrent RRD. Compared with the reattachment group, the recurrence group exhibited a significant decline in best-corrected visual acuity (BCVA) at the last follow-up visit (P = 0.000). Eyes with PVR prior to primary surgery, or at the diagnosis of re-detachment, showed a worse final BCVA. Our analysis shows that the predominant risk factor for the recurrence of RRD is a PVR ≥ Grade C. PVR prior to primary surgery, or at the diagnosis of re-detachment, was also shown to limit the recovery of final visual acuity.

Three-Year Outcomes of Intravitreal Aflibercept Injections for Retinal Angiomatous Proliferation According to Disease Stage.

IntroductionTo evaluate the outcomes of intravitreal aflibercept injections for retinal angiomatous proliferation (RAP) according to disease stage.MethodsThis retrospective chart review included 68 eyes of 53 individuals diagnosed as having RAP and 109 neovascular age-related macular degeneration (nAMD) eyes of 109 patients as controls. All patients received intravitreal injections of aflibercept in a real-world setting. The main outcome measures were the changes in the mean of best-corrected visual acuity (BCVA) and central retinal thickness (CRT) as well as the total number of injections received during the 3-year follow-up period.ResultsThe average BCVA and CRT changes in eyes affected by RAP and the controls at 3 years were non-significant. Both populations received a similar number of injections. After 3 years of treatment, patients with RAP had visual decline despite stable anatomical outcomes. Approximately 50% of the eyes with stage II RAP exhibited significant BCVA decline at the end of the third year. Among those eyes that had deteriorated BCVA, persistently worsening BCVA and thinning CRT were observed from year 2 to year 3.ConclusionSimilar to treating nAMD, intensive injections or aggressive treatment strategies are required to treat RAP to achieve optimal visual outcomes in a real-world setting. The response to aflibercept treatment at the second year is associated with the final visual outcome of eyes with stage II RAP lesions.

P13: CAN PATIENT-REPORTED OCULAR SYMPTOMS GUIDE DOSE MODIFICATIONS IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA RECEIVING BELANTAMAB MAFODOTIN?

Introduction: Belantamab mafodotin (belamaf) is a B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate approved as a monotherapy for triple-class refractory adult patients with relapsed/refractory multiple myeloma (RRMM). This hypothesis generating post hoc analysis of DREAMM-2 trial (NCT03525678) data examined relationships between corneal exam findings, best-corrected visual acuity (BCVA) changes and direct patient-reported ocular symptoms per the Ocular Surface Disease Index (OSDI) questionnaire. This approach may provide insight into relationships between corneal exam findings, BCVA, ocular symptoms, impact on quality of life to determine if BCVA decline and symptoms can guide dosing. Surrogate marker identification for results from corneal exam findings would help providers determine if dosing adjustments are necessary. Methods: Snellen chart BCVA assessment and corneal eye exams were performed on all patients receiving belamaf (2.5 mg/kg, q3w) by ECPs at baseline (BL) and before each dose. Corneal exam findings (keratopathy) and BCVA were assessed per protocol-defined criteria. Grade (GR) assessment, relative to BL, was based on the worst finding in the worse eye. Patient-reported ocular symptoms and vision-related functioning, as per the OSDI, were used to evaluate the impact of treatment-related ocular toxicity. The OSDI patient-reported outcome questionnaire assesses eye symptoms/effects on vision-related function and was performed in all patients before each belamaf dose. Items 1–5 address the frequency of eye-related symptoms and items 6–9 address functional limitation frequency. OSDI was considered positive, clinically meaningful and potentially treatment associated when at least one question 1–5 (sensitivity to light, gritty/painful eyes, blurred or poor vision) was reported as experienced “all of the time” and at least one question 6–9 (driving at night, reading, working with PC or watching TV) was reported as experienced “most of the time.” Results: GR 3–4 (severe) keratopathy was observed 5% of the time in patients not reporting frequent ocular symptoms measured by the OSDI questionnaire (no items 1–9 ≥ “most of the time”). In patients who reported no items 1–5 “all of the time” AND no items 6–9 ≥ “most of the time” (OSDI negative), GR 3–4 keratopathy was observed 6.5% of the time (Table). In patients who reported “no deterioration from BL” for any OSDI eye-related symptoms or functional limitations, GR 3–4 keratopathy was observed ~3%–7% of the time and GR 0–2 (mild) keratopathy ~23%–34% of the time. Similar results were observed in patients with BL BCVA ≤20/30 who reported “no deterioration from BL” for any eye-related adverse events (AEs) or functional limitations (GR 3–4 keratopathy: ~2%–6% of the time; GR 0–2 keratopathy: ~19%–28% of the time); patients with worse BL visual acuity (BCVA >20/30) who reported “no deterioration” for items 1–9 had lower incidence of GR 3–4 (~0%–1%) and GR 0–2 keratopathy (~3%–8%). Conclusions: These results suggest that hematologists/oncologists may be able to use ocular symptoms and the OSDI tool as potential surrogate markers for eye exam results to help determine whether dosing changes are needed. Validation with other belamaf dose regimens is ongoing. Funding Source: GSK(205678) Encore statement: Previously presented as Poster 2746 at the American Society of Hematology Annual Meeting, 11–14 December 2021; submitted with permission and on behalf of the original authors.