Outcomes of Treatment-Resistant Neovascular Age-Related Macular Degeneration Switched from Aflibercept to Faricimab.

PURPOSE: Although previous studies have demonstrated the efficacy of faricimab in treatment-naive patients with neovascular age-related macular degeneration (nAMD), its outcomes in patients switched from aflibercept are less understood. This study aimed to assess clinical anatomical and functional outcomes of switching to faricimab in patients undergoing aflibercept intravitreal injections (IVIs) for nAMD with suboptimal response. DESIGN: Retrospective case series. SUBJECTS: Patients with nAMD at a single tertiary care center who were switched from aflibercept to faricimab due to persistent suboptimal response. METHODS: Patients had received a minimum of 6 consecutive IVIs of aflibercept and showed persistent presence of intraretinal (IRF) or subretinal fluid (SRF) on OCT despite receiving aflibercept at 4 or 6-weekly intervals at the time of the switch. Patients receiving 4-weekly aflibercept were switched with either 2 or 3 loading doses of 4-weekly faricimab injections. Regression models were used to identify predictors of clinical outcomes. MAIN OUTCOME MEASURES: Visual acuity, central macular thickness (CMT), and OCT parameters were assessed preswitch and postswitch. RESULTS: Eighty-one eyes of 68 patients were included. The mean age was 79.1 years (standard deviation: 8.9), and females constituted 53% of cases. A statistically significant reduction in CMT was observed postswitch (P < 0.0001). The proportion of cases with IRF (P = 0.0219) and SRF (P < 0.000) decreased significantly. Overall clinical improvement on OCT was noted in 80% of patients. No significant improvement in ETDRS vision was observed. There was no evidence that switching regimen (2 vs. 3 loading doses) had an independent effect on clinical outcomes. CONCLUSION: Among patients with treatment-resistant nAMD, switching from aflibercept to faricimab may serve as a safe and effective option. Significant anatomical improvements were observed, with a trend toward visual stability. The loading regimen with 2 faricimab injections appeared to be sufficient for nonnaive patients. However, a longer follow-up and larger studies are warranted to confirm these findings. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Correction: Diabetic retinopathy and diabetic macular oedema pathways and management: UK Consensus Working Group.

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Diabetic retinopathy and diabetic macular oedema pathways and management: UK Consensus Working Group.

The management of diabetic retinopathy (DR) has evolved considerably over the past decade, with the availability of new technologies (diagnostic and therapeutic). As such, the existing Royal College of Ophthalmologists DR Guidelines (2013) are outdated, and to the best of our knowledge are not under revision at present. Furthermore, there are no other UK guidelines covering all available treatments, and there seems to be significant variation around the UK in the management of diabetic macular oedema (DMO). This manuscript provides a summary of reviews the pathogenesis of DR and DMO, including role of vascular endothelial growth factor (VEGF) and non-VEGF cytokines, clinical grading/classification of DMO vis a vis current terminology (of centre-involving [CI-DMO], or non-centre involving [nCI-DMO], systemic risks and their management). The excellent UK DR Screening (DRS) service has continued to evolve and remains world-leading. However, challenges remain, as there are significant variations in equipment used, and reproducible standards of DMO screening nationally. The interphase between DRS and the hospital eye service can only be strengthened with further improvements. The role of modern technology including optical coherence tomography (OCT) and wide-field imaging, and working practices including virtual clinics and their potential in increasing clinic capacity and improving patient experiences and outcomes are discussed. Similarly, potential roles of home monitoring in diabetic eyes in the future are explored. The role of pharmacological (intravitreal injections [IVT] of anti-VEGFs and steroids) and laser therapies are summarised. Generally, IVT anti-VEGF are offered as first line pharmacologic therapy. As requirements of diabetic patients in particular patient groups may vary, including pregnant women, children, and persons with learning difficulties, it is important that DR management is personalised in such particular patient groups. First choice therapy needs to be individualised in these cases and may be intravitreal steroids rather than the standard choice of anti-VEGF agents. Some of these, but not all, are discussed in this document.

Anatomical and functional outcomes following switching from aflibercept to ranibizumab in neovascular age-related macular degeneration in Europe: SAFARI study.

BACKGROUND/AIMS: Prospective data on switching anti-vascular endothelial growth factors in patients with neovascular age-related macular degeneration (nAMD) who have previously shown no/partial response are limited. This prospective study assessed the effect of switching from aflibercept to ranibizumab on anatomical and functional outcomes in patients with persistent/recurrent disease activity. METHODS: SAFARI (NCT02161575) was a 6-month, prospective, single-arm study conducted in the UK and Germany. Patients, meeting strict eligibility criteria for one of two subgroups (primary treatment failure or suboptimal treatment response), received 3 monthly intravitreal ranibizumab injections (0.5 mg). Thereafter, ranibizumab was administered pro re nata at monthly visits. The primary endpoint was change from baseline (CfB) to day 90 in central subfield retinal thickness (CSRT). Best-corrected visual acuity (BCVA) and retinal morphology parameters were assessed. RESULTS: One hundred patients were enrolled (primary treatment failure, 1; suboptimal treatment response, 99). In the overall population, there was a significant CfB in median CSRT of -30.75 µm (95% CI -59.50,-20.50; p<0.0001) to day 90. Improvements were also observed in other quantitative and qualitative optical coherence tomography parameters. In Early Treatment Diabetic Retinopathy Study letters assessed by category, 55% and 59% of patients gained 0-≥15 letters versus baseline at day 90 and day 180, respectively. However, mean improvements in BCVA (CfB) to each time point were small (≤2 letters). No new safety signals were identified. CONCLUSION: Switching from aflibercept to ranibizumab led to a significant improvement in CSRT, with ~60% experiencing stabilised/improved BCVA. Therefore, patients with nAMD who have shown a suboptimal response to aflibercept may benefit from switching to ranibizumab.

Viscogonioplasty in narrow angle glaucoma: a randomized controlled trial.

PURPOSE: To determine the effect of viscogonioplasty and cataract extraction on intraocular pressure in patients with narrow angle glaucoma. METHODS: This was a double-masked randomized controlled trial involving 50 eyes (25 cases and 25 controls) from 38 consecutive patients. All patients underwent phacoemulsification with or without viscogonioplasty. The main outcome measures were intraocular pressure post-treatment and number of glaucoma medications post-treatment. RESULTS: Cases had a greater reduction in intraocular pressure than controls, with a mean intraocular pressure (standard deviation) at 12 months of 13.7 (±2.89) mmHg compared with 16.2 (±3.55) mmHg in controls (P = 0.009). Cases had a greater reduction in mean number of antiglaucoma medications than controls at 12-month review, with 13 of 25 eyes (52%) of cases controlled without any antiglaucoma therapy versus 9 of 25 (36%) of the controls (P = 0.005). CONCLUSIONS: Viscogonioplasty combined with cataract extraction has a significantly greater effect than cataract extraction alone on lowering intraocular pressure in patients with poorly controlled narrow angle glaucoma and should therefore be considered as a treatment option for patients with this condition.

Gangrene intestine caused by Ascaris lumbricoides; report of 5 cases in children.

Ascaris infestation in the gastrointestinal tract is well known in Asian countries. It can be asymptomatic or can present with symptoms of acute abdomen. Perforation and torsion with gangrene are its very rare fatal complications but an important cause of mortality in children. Although ascariasis is very rare in developed countries, clinicians should consider this potentially dangerous, yet treatable, infection in the differential diagnosis of acute abdomen. We herein report a series of five cases of intestinal gangrene secondary to extensive infestation by Ascaris lumbricoides in children aged 1-4 years.

Role of p53 and bcl2 as markers of vitamin A response in premalignant lesions of the oral cavity.

Oral cancer accounts for 40 to 50% of cancers diagnosed in India. Oral cancer is preceeded in most cases by pre malignant lesions-leukoplakia, submucous fibrosis and lichen planus. Stoppage of causative agents reverts premalignant lesions in some of the cases only. Thus anti oxidant therapy is being used to revert premalignant change to normal. Few studies available, have taken clinical parameters as indicators of response to therapy. Extensive medline search failed to reveal any study at the cellular level. This study attempts to investigate for the first time the role of p53 and bcl2 as markers of prognosis following vitamin A therapy. 24 cases of pre malignant lesions of oral cavity were studied. 1 lakh IU of vitamin A were given orally twice a week for 3 months. Biopsies were done before and after therapy. Haematoxylin and Eosin stain was done to confirm diagnosis. Immunostaining for mutant p53 and bcl2 was done on paraffin sections. 500 cells were counted over an average of 5 HPF and percentage positivity was calculated. Statistical analysis was done by applying the paired t tests. In 19 cases (79.2%) of premalignant lesions mutant p53 expression was zero before therapy, and remained unchanged even after the therapy. 3 cases (12.5%) had high mutant p53 values which reduced following therapy (p = 0.037). Therapy thus proved effective in these cases. However, in 2 cases (8.3%) pre therapy values of zero showed an increase after vitamin A therapy. These were the cases which had dysplasia and were chronic smokers. In 2 cases (8.3%) pre therapy values of bcl2 were zero and remained unchanged even after therapy and these cases did not stop smoking even during the vitamin A therapy. In 12 cases (50.0%) higher pre therapy values were reduced after therapy (p < 0.0001). Vitamin A therapy was effective in these cases. However, in 10 cases (42.0%) expression of bcl2 increased subsequent to therapy. Therapy failed in these cases because of chronic heavy smoking and tobacco chewing. Thus, in the majority of cases vitamin A was effective in preventing mutation of p53 (91.7%) and expression of bcl2 (58.0%). In effect, these two oncoproteins can be used as prognostic markers and follow up for anti oxidant therapy.

A case series on chronic canaliculitis.

INTRODUCTION: Primary chronic canaliculitis is an uncommon disease, which is often misdiagnosed and insufficiently treated. We present two cases of canaliculitis caused by two different organisms, Actinomycetes spp. and Arcanobacterium haemolyticum. To the best of our knowledge, canaliculitis due to Arcanobacterium haemolyticum has not been reported before. PATIENTS AND METHODS: The two cases described in this series show typical clinical features of canaliculitis with an inflamed upper canaliculus, not responsive to topical antibiotics. Appropriate treatment was delayed as they were initially treated for conjunctivitis. Both patients were treated with a canaliculotomy, with curettage and subsequent treatment with topical and systemic penicillin. The contents were sent for microbiological examination. RESULTS: There was complete resolution following treatment. Actinomyces spp. was grown from one patient as expected. However, in the second patient, Arcanobacterium haemolyticum was isolated. Although this organism was not expected, the patient did respond to similar, conventional treatment. DISCUSSION: Actinomyces spp. is a cast-forming Gram-positive anaerobe. They are difficult to isolate and identify and can cause infections of hollow spaces with formation of canaliculiths. Arcanobacterium (Corynebacterium) haemolyticum closely resembles Actinomyces (Corynebacterium) pyogenes. Ocular infections reported with this organism include orbital cellulitis and subperiosteal abscesses. The difficulty encountered in the isolation and identification of these organisms is discussed and the need for thorough curettage in the treatment of persistent or recurrent canaliculitis is emphasised. CONCLUSION: Chronic canaliculitis should be considered in any patient who presents with chronic or recurrent conjunctivitis. Definitive cure will not be affected until all concretions are removed, either at surgery or by mechanical expression.

Mesenteric cystic lymphangiomas--a report of five cases.

Five cases of cystic lymphangiomas are described. There were three children and two adult patients. Age ranged from 4 to 38 years. All the patients presented with pain abdomen. On examination, four out of five patients were found to have an ill defined lump abdomen. One patient had no abdominal symptoms. Abdominal ultrasonography done in all the cases revealed the cystic nature of the tumour thereby making the pre operative diagnosis easier. A histological diagnosis of cystic mesenteric lymphangioma was made in each case. Although mesenteric lymphangiomas are rare, they should be considered as a possible cause of acute abdomen, both in children and adults.

Gamna Gandy bodies of spleen seen in CML: a causal association--a case report.

Gamna Gandy bodies are usually seen in spleen in cases of chronic venous congestion. We present a case of CML showing gamna gandy bodies. These may have occurred as a part of evolving portal hypertension which maybe due to antileukemic therapy or CML per se or due to a combination of both factors.