Efficacy and safety of faricimab for neovascular age-related macular degeneration: a systematic review and network meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of faricimab compared with other anti-vascular endothelial growth factor (anti-VEGF) agents in treating neovascular age-related macular degeneration (nAMD) patients. METHODS AND ANALYSIS: A systematic review (SR) was conducted up to January 2023. Network meta-analyses (NMA) were performed, including sensitivity and subgroup analyses for naïve population. Outcomes included changes in visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] letters), anatomical changes, frequency of injections and adverse events. The Cochrane Collaboration guidelines and the Confidence in Network Meta-Analysis framework were used for the SR and the certainty of evidence, respectively. RESULTS: From 4128 identified records through electronic databases and complementary searches, 63 randomised controlled trials (RCTs) met the eligibility criteria, with 42 included in the NMA. Faricimab showed a significant reduction in the number of annual injections compared with most fixed and flexible anti-VEGF treatment regimens, while showing no statistically significant differences in visual acuity through ETDRS letter gain, demonstrating a comparable efficacy. Retinal thickness results showed comparable efficacy to other anti-VEGF agents, and inferior only to brolucizumab. Results also showed that more patients treated with faricimab were free from post-treatment retinal fluid compared with aflibercept every 8 weeks, and both ranibizumab and bevacizumab, in the fixed and pro re nata (PRN) assessed schedules. Faricimab showed a comparable safety profile regarding the risk of ocular adverse events and serious ocular adverse events (SOAE), except for the comparison with brolucizumab quarterly, in which faricimab showed a significant reduction for SOAE risk. CONCLUSION: Faricimab showed a comparable clinical benefit in efficacy and safety outcomes, with a reduction in annual injections compared with fixed and flexible anti-VEGF drug regimens, representing a valuable treatment option for nAMD patients. PROSPERO REGISTRATION NUMBER: CRD42023394226.

Short-chain cyanoacrylates and long-chain cyanoacrylates (Dermabond) have different antimicrobial effects.

OBJECTIVE: To compare the antimicrobial effect in vitro of a short-chain cyanoacrylate with a long-chain cyanoacrylate (Dermabond, Ethicon, Johnson and Johnson, USA) against bacterial strains. METHODS AND ANALYSIS: The following bacterial strains were analysed: Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa. For each microorganism, standardised sterile discs (6 mm) containing 10 µL of ethyl-cyanoacrylate and 2-octyl cyanoacrylate were applied to the plate. All plates received a blank filter-paper disc with no adhesive (control). All plates were incubated for 24 hours, after which the bacterial inhibitory halos, if present, were measured in millimetres in its greater length. RESULTS: Inhibitory halos were observed for both adhesives for S. aureus. Inhibition halos were observed only for ethyl-cyanoacrylate for K. pneumoniae and E. coli. No inhibition halo was observed for P. aeruginosa in any sample. The relationship between the total size of the inhibition halos and the diameter of the paper filter for S. aureus was statistically significant compared with 2-octyl cyanoacrylate. CONCLUSION: Data shown conclude that ethyl-cyanoacrylate showed in vitro bacteriostatic activity for S. aureus, E. coli and K. pneumoniae. 2-Octyl cyanoacrylate showed in vitro lower bacteriostatic activity only against S. aureus when compared with ethyl-cyanoacrylate. No in vitro bactericidal activity of ethyl-cyanoacrylate or 2-octyl cyanoacrylate was observed.

Impact of Inflammation and Treatment on Self-reported Quality of Life in Patients with Non-acute Vogt-Koyanagi-Harada Disease (VKHD).

Aims: To evaluate associations between vision-related (VR-) and health-related (HR-) QoL metrics and inflammation and treatment in non-acute VKHD patients.Methods: Cross-sectional study in a tertiary center in Sao Paulo, Brazil with 22 patients with non-acute VKHD followed prospectively for ≥12 months since acute disease onset, with systematic evaluation and predefined treatment protocols. VR- and HR-QoL aspects were assessed by VFQ-25 and SF-36 questionnaires, respectively. Associations between the questionnaire's subscale item scores with inflammation and systemic medical therapies were assessed.Results: After generalized linear model analysis, worse VA, severe fundus changes, fluctuation of VA and fluctuation of anterior chamber cells impacted negatively on VR-QoL items. Higher cumulative total dose of corticosteroids and use of immunosuppressive therapy impacted negatively on both questionnaires.Conclusion: Worse VA, clinical inflammation and systemic treatment have a significant impact on VR- and HR-QoL questionnaires. Subclinical choroidal inflammation did not seem to impact QoL.

Impact of calcification and infrapopliteal outflow on the outcome of endovascular treatment of femoropopliteal occlusive disease.

OBJECTIVES: In this paper, we report the long-term outcomes of the endovascular treatment of femoropopliteal occlusive disease, focusing on the importance of calcification and runoff outflow on limb salvage and patency, and the factors associated with these outcomes at a single center. METHODS: This retrospective cohort study included consecutive patients with femoropopliteal occlusive who underwent femoropopliteal angioplasty at the Division of Vascular and Endovascular Surgery, Hospital do Servidor Público Estadual, São Paulo, Brazil, between January 2015 and July 2017. RESULTS: In total, 86 femoropopliteal occlusive angioplasties were performed in 86 patients, with an initial technical success rate of 95.34%. The mean ± standard deviation follow-up time was 880 ± 68.84 days. The analysis was performed at 720 days. Technical failure occurred in four patients, who were excluded from the analysis, leaving 82 patients and 82 femoropopliteal occlusive angioplasties. The estimated primary patency, secondary patency, limb salvage, and overall survival rates at 720 days were 60%, 96%, 90%, and 82.5%, respectively. In univariate and multivariate analyses, Cox regression showed worse primary patency rates in patients with one tibial vessel or isolated popliteal artery runoff (p = 0.005), calcification grade 4 (p = 0.019), calcification grade > 2 (p = 0.017), small vessel diameter < 4 mm (p = 0.03) or primary angioplasty without stenting (p = 0.021). A univariate analysis showed worse limb salvage in patients with one tibial vessel or isolated popliteal artery runoff (p = 0.039). CONCLUSIONS: In this study, the main factors associated with worse outcomes in the endovascular treatment of femoropopliteal occlusive in terms of loss of primary patency were one tibial vessel or isolated popliteal artery runoff, calcification grade 4, or calcification grade > 2, small vessel diameter < 4 mm, and no stents use. One tibial vessel or isolated popliteal artery runoff was also associated with limb loss in a univariate Cox regression analysis.

Clinical features of paediatric uveitis at a tertiary referral centre in São Paulo, SP, Brazil.

AIMS: To analyse the clinical features, systemic associations, treatment and visual outcomes of uveitis in children from a referral centre in São Paulo, Brazil. METHODS: Clinical records of patients under 16 years old who attended the Uveitis Service, Hospital das Clinicas, Faculdadede Medicina, Universidade de São PauloFMUSP, between April and September 2017, were reviewed retrospectively. Patients with incomplete medical records, previous ocular trauma, or less than six6 months of follow-up were excluded. RESULTS: Thirty-nine children (25 female/14 male) were included. There was predominance of bilateral (89.7%), asymptomatic (56.4%) and recurrent/chronic cases (84.6%). The mean age at study inclusion was 10.7±3.4 years (range 3-16 years). Improvement or preservation of visual acuity (VA) was observed in 27 patients (84%); VA was not informed in 8 patients. Patients were referred early to tertiary centre (55% within 6 months of uveitis diagnosis). Anterior uveitis was the most common involvement (46%), followed by intermediate uveitis (26%). Juvenile idiopathic arthritis (JIA)-associated uveitis (41%) and immune-mediated intermediate uveitis (25.6%) were the principal non-infectious conditions; ocular toxoplasmosis (7.7%) and toxocariasis (5.1%) were the most common infectious conditions. Ocular complications were observed at first visit in 46% of patients and in 90% during final evaluation. Oral prednisone, immunosuppressive therapy (IMT) and/or biologic agents were used in all non-infectious conditions (32 children, 82%); IMT and/or biologic agents were used in all patients with JIA-associated uveitis and in 50% of patients with immune-mediated intermediate uveitis. CONCLUSION: Paediatric patients with uveitis are referred early to this centre and, although severe, adequate management with systemic IMT may preserve VA.

Comparison among adjuvant treatments for primary pterygium: a network meta-analysis.

PURPOSE: Pterygium is a frequent ocular disease, where the major challenge is the high level of recurrence after its surgical removal. We performed a network meta-analysis to identify, among several adjuvant treatments for primary pterygium, which is the best to prevent recurrence. METHODS: A search was conducted using PubMed, Scientific Electronic Library Online, Latin American and Caribbean Centre on Health Sciences and Cochrane Eyes and Vision Group Trials Register between 1993 and 2015 for randomisedclinical trials (RCTs) comparing adjuvant treatments following primary pterygium surgery. RESULTS: 24 RCTs that studied 1815 eyes of 1668 patients were included and allowed direct and indirect comparison among 14 interventions through network meta-analysis. The rank from the best to worse treatment to prevent recurrence is: conjunctival autograft + ciclosporin 0.05% eye drops, bare sclera + intraoperativemitomycin C (MMC) <0.02%, bare sclera + beta therapy (2500 cGy single dose), conjunctival autograft + beta therapy (1000 cGy single dose), bare sclera + MMC 0.02% eye drops, conjunctival autograft, bare sclera + intraoperative MMC >0.02%, bare sclera + ciclosporin 0.05% eye drops, bare sclera + intraoperative 5-fluorouracil 5%, amniotic membrane transplantation, bare sclera + intraoperative MMC 0.02%, conjunctival autograft + bevacizumab 0.05% eye drops, bare sclera + bevacizumab 0.05% eye drops and bare sclera alone. CONCLUSION: The best adjuvant treatment to prevent recurrence after primary pterygium surgery is the association of conjunctival autograft and ciclosporin 0.05% eye drops. Bare sclera technique alone should be discontinued since it is associated with high recurrence rates.

Assessment of retinoblastoma RNA reflux after intravitreal injection of melphalan.

BACKGROUND: Intravitreal injection of chemotherapy in retinoblastoma eyes with vitreous seeds may lead to a risk of extraocular tumour dissemination that has not been assessed so far. AIMS: To develop a sensitive and clinically feasible technique to assess for potential retinoblastoma cell reflux after intravitreal injection of melphalan. METHODS: Filter papers were cut in 6 mm diameter circles and sterilised before use. Eyes with retinoblastoma vitreous seeds (group D, International Classification) received weekly intravitreal melphalan injections (20 µg or 30 µg/dose) followed by cryotherapy as part of local treatment. Immediately after finishing the injection and cryotherapy, filter papers were placed on the injection site and on the cryoprobe tip to assess for the expression of the cone-rod homeobox gene (CRX) by real-time qPCR as a surrogate of retinoblastoma RNA. The assay was developed and validated to determine sensitivity, linearity, recovery, repeatability and reproducibility. RESULTS: The assay for quantitation of CRX expression was linear in the range of 1 to 1000 cells. The lowest limit of detection was one retinoblastoma cell and allowed to recover 100% of the cell load in external supplementation. A total of 14 eyes received 22 cycles of intravitreal melphalan and were evaluated for potential extraocular tumour cell dissemination using the developed technique. None of the cycles were positive for CRX in samples from the scar or from the cryoprobe tip. CONCLUSIONS: A sensitive and simple method of tumour cell assessment has been developed that can be used in the clinics to assess for potential extraocular dissemination after intravitreal injections to assure its performance.

Non-traumatic corneal perforations: aetiology, treatment and outcomes.

PURPOSE: To report aetiology, characteristics, treatment and main outcomes of non-traumatic corneal perforations in a single referral centre. METHODS: A retrospective review of clinical records of patients diagnosed with non-traumatic corneal perforation. The analysed data included demographic characteristics, medical history, initial and final corrected distance visual acuity (CDVA), perforation aetiology, size, location, initial therapy, surgical treatment, ocular integrity and complications. A comparison between non-infectious and infectious groups was performed. Different variables were analysed through a multiple logistic regression analysis for the probability to have at least one more procedure. RESULTS: We included 127 eyes of 116 patients with a mean age of 50 years and a mean follow-up of 11 months. The initial CDVA was 3.00 logarithm of the minimum angle of resolution (logMAR) and the final CDVA was 2.30 logMAR (p>0.5). Regarding treatment, of the 49 eyes with an initial cyanoacrylate patch, 35 eyes (71.4%) had at least one more procedure performed (p>0.001). In comparison, of the 49 eyes with an initial tectonic penetrating keratoplasty (PK), 33 (67.3%) eyes remained stable while 16 (32.7%) eyes needed one or more interventions (p=0.004). In a multiple logistic regression analysis, an initial cyanoacrylate patch represented a probability of 4.7 times to require a subsequent procedure in comparison with an initial PK. Overall, globe integrity was achieved in 96.1% of the cases. CONCLUSIONS: Corneal perforations represent an important cause of ocular morbidity. The use of a cyanoacrylate patch is useful as an initial therapy in corneal perforations; however, procedures such as PK are often necessary to achieve anatomical success, especially in non-infectious aetiologies.

Influence of involuntary eyelid spasms on corneal topographic and eyelid morphometric changes in patients with hemifacial spasm.

BACKGROUND/AIMS: In patients with hemifacial spasm (HFS), treatment relieves eyelid spasms on the affected side, thus changes in corneal topography and eyelid morphometry may be observed after treatment. We aimed to evaluate these parameters during a 4-month period in patients with HFS treated with botulinum toxin A (BTX-A). METHODS: This prospective study evaluated eyelid morphometric and corneal topographic changes in patients with HFS before onabotulinum toxin A application, and after 15 days and 2, 3 and 4 months. RESULTS: 24 patients were treated with BTX-A. On the normal side, the mean palpebral fissure height (PF), interpalpebral surface area (ISA), steep K and astigmatism values were 8.7±1.98 mm, 122.09±39.37 mm2, 44.99±1.45 D and 0.9±0.64 D, respectively, before treatment. A statistically significant difference was not observed in these parameters after treatment (p>0.05). On the affected side, the mean PF, ISA, steep K and astigmatism were 5.5±1.77 mm, 67.68±28.49 mm2, 46.91±3.57 D and 2.63±2.46 D, respectively, before treatment. We observed a statistically significant (p<0.05) increase in the mean PF and ISA on the affected side 15 days (8.36±1.91 mm and 115.92±34.44 mm2, respectively), 2 months (8.18±1.80 mm and 112.22±33.57 mm2, respectively) and 3 months (7.27±1.65 mm and 95.48±27.80 mm2, respectively) after treatment. A statistically significant decrease in steep K and astigmatism was observed at 2 months (45.14±1.20 D and 1.01±0.58 D, respectively) and 3 months (45.64±1.77 D and 1.36±1.31 D, respectively) after treatment. CONCLUSIONS: The results suggest that treatment with BTX-A in patients with HFS leads to eyelid and corneal changes on the affected eye that are significant during the known period of action of the toxin. Thus, caution should be taken when performing ophthalmological examination in patients with HFS, since it may vary according to BTX-A period of action.

Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration.

BACKGROUND/AIMS: Real-life anti-vascular endothelial growth factor (VEGF) therapy use in patients with wet age-related macular degeneration (wAMD) was assessed in a retrospective, observational study in Canada, France, Germany, Ireland, Italy, the Netherlands, UK and Venezuela. METHODS: Medical records of patients with wAMD, who started ranibizumab treatment between 1 January 2009 and 31 August 2009, were evaluated. Data were collected until the end of treatment and/or monitoring or until 31 August 2011. RESULTS: 2227 patients who received ≥1 anti-VEGF injection with a baseline visual acuity assessment and ≥1 postbaseline visual acuity assessment for the treated eye were evaluated. Visual acuity improved until about day 120; thereafter, visual acuity gains were not maintained. Mean change in visual acuity score from baseline to years 1 and 2 was +2.4 and +0.6 letters, respectively. Patients received a mean of 5.0 and 2.2 injections in the first and second year, respectively. There were substantial differences in visual outcomes and injection frequency between countries. More frequent visits and injections were associated with greater improvements in visual acuity. CONCLUSIONS: In clinical practice, fewer injections are administered than in clinical trials. Anti-VEGF treatment resulted in an initial improvement in visual acuity; however, this was not maintained over time. TRIAL REGISTRATION NUMBER: NCT01447043.

Contrast sensitivity evaluation in high risk proliferative diabetic retinopathy treated with panretinal photocoagulation associated or not with intravitreal bevacizumab injections: a randomised clinical trial.

PURPOSE: To compare the effect on contrast sensitivity (CS) measurements of panretinal photocoagulation (PRP) associated with intravitreal bevacizumab (IVB) injections versus PRP alone in high risk proliferative diabetic retinopathy (HR-PDR). DESIGN: Prospective, randomised, masked, controlled trial. PARTICIPANTS: 42 patients with HR-PDR with visual acuity ≥20/200. METHODS: Eyes were randomised to one of two groups: one underwent PRP and IVB injections (study group) and the other PRP alone (control group). PRP was performed three times during the study and IVB injection was administered twice. MAIN OUTCOME MEASURES: Mean change in CS threshold scores between and within groups, from baseline to 6 months. RESULTS: Seven patients presented with vitreous haemorrhage and were removed from the study. Mean results for CS threshold (at 1.5, 3, 6, 12 and 18 cycles per degree (cpd) frequencies) for patients with and without diabetic macular oedema showed no significant differences (p>0.05 for all comparisons) between the two groups. In 35 eyes in the control group, compared with baseline values, there was significant worsening (p<0.05) of CS at 1.5, 12 and 18 cpd after 1 month, at 12 cpd after 3 months, and at 6 and 12 cpd after 6 months. In the study group, there was significant improvement in CS at 3 cpd, 3 months after treatment. CONCLUSIONS: In eyes with HR-PDR, PRP treatment is associated with deterioration of CS while adjuvant use of bevacizumab prevents such deterioration. CS evaluation seems to support the adjuvant use of bevacizumab when using PRP for the treatment of HR-PDR. ClinicalTrials.gov Identifier NCT 01389505.