Safety and efficacy of Razumab™ (world's first biosimilar ranibizumab) in wet age-related macular degeneration: a post-marketing, prospective ASSET study.

BACKGROUND: Razumab™ (world's first biosimilar ranibizumab) is approved for several macular disorders including wet age-related macular degeneration (AMD). We evaluated the safety and efficacy of biosimilar ranibizumab in wet AMD. METHODS: This prospective, multicentre, rAnibizumab bioSimilar Safety Efficacy postmarkeTing (ASSET) study enrolled patients aged ≥ 50 years with wet AMD having best-corrected visual acuity (BCVA) between 20/40 and 20/320. The patients received intravitreal biosimilar ranibizumab 0.5 mg every 4 weeks for 24 weeks. Safety endpoints included the incidence of adverse events (AEs), serious AEs (SAEs), and immunoreactivity after 6 months. The efficacy endpoints were the proportion of patients who lose fewer than 15 letters, increase in BCVA, change in central retinal thickness (CRT), and change in Visual Function Questionnaire-25 (VFQ-25) score, from baseline to 24 weeks. RESULTS: Of the 126 enrolled patients, majority (95.24%) of the patients received all 6 doses of biosimilar ranibizumab (total 3 mg). Nineteen AEs were reported (n = 16; 12.7%); majority (78.9%) were mild. There were no serious AEs reported, except one AE of death which was unrelated to the study drug. None of the patients discontinued the study due to an AE. The most common ocular AE was increase in intraocular pressure (4 events) and non-ocular AE was pyrexia (5 events). A total of 7.9% (10/126) patients prior to dosing and 7.1% (9/126) patients post-treatment were positive for anti-ranibizumab antibodies. No AEs suggestive of immunogenicity were noted. At 24-weeks, 97.60% patients in the intent-to-treat (ITT) population (N = 125) and 97.41% patients in the per-protocol (PP) population (N = 116) lost < 15 letters from baseline visual acuity. In the ITT and PP populations, 31.20% and 32.76% patients, respectively, showed improved visual acuity by ≥ 15 letters. Significant improvements in BCVA (mean difference: 8.8, 9.2, p < 0.001 for ITT, PP) and VFQ-25 (8.5, 9.2, p < 0.001 for ITT, PP) were seen; CRT reduced significantly (125 µm, 119.3 µm, p < 0.001 for ITT, PP). CONCLUSION: Razumab™ (world's first biosimilar ranibizumab) was well-tolerated without new safety concerns and significantly improved visual acuity in wet AMD patients. Trial registration CTRI/2016/03/006739. Registered 18 March 2016-Prospectively registered, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=13141&EncHid=&userName=2016/03/006739.

Association between Diabetic Retinopathy and Chronic Periodontitis-A Cross-Sectional Study.

Periodontal disease (PD), a chronic inflammatory condition characterized by destruction of the supporting tissues of the teeth, increases the risk of complications in diabetics. Diabetic retinopathy (DR) is a microvascular complication of prolonged hyperglycaemia. There appears to be a similarity in the pathogenesis of DR and PD. Hence, this study aimed to investigate the association, if any, between DR and PD, correlate the severity of DR with the severity of PD, and investigate the association between glycated haemoglobin (HbA1c), serum creatinine and periodontal variables. The periodontal status of 200 adult diabetic patients in the age group of 30⁻65 years with varying severity of DR was assessed. Evaluation of the severity of PD was assessed by recording clinical parameters. Haematological investigations including glycated haemoglobin (HbA1c) and serum creatinine were estimated before the initiation of treatment for DR. A statistically significant association between the mean duration of diabetes mellitus (DM) and the severity of DR and PD was found. The severity of PD was directly correlated with the severity of DR. There was a significant association between the levels of HbA1c and serum creatinine and severity of DR and PD. There could be a plausible relationship between DR and PD. Further prospective studies on a larger population with longer follow-ups are required to ascertain whether PD and its severity directly affect the progression and severity of DR.

Autosomal recessive bilateral frontal polymicrogyria with ectopia lentis and chorioretinal dystrophy.

Polymicrogyria is a type of cortical dysplasia with cortical organizational defect. Bilateral polymicrogyria are distinct with genetic basis in a subset. We hereby report a case of bilateral frontal polymicrogyria (BFP) in association with chorioretinal dystrophy and ectopia lentis (EL) in a 26-year-old lady born of a consanguineous parentage. Her male sibling also had chorioretinal dystrophy and EL. This combination of autosomal recessive inheritance has not been reported earlier in the literature and suggests a role of connective tissue genes in BFP.

Subretinal worm and repeat laser photocoagulation.

Diffuse unilateral subacute neuroretinitis (DUSN) can be a diagnostic dilemma. Laser photocoagulation of the subretinal worm is an effective treatment for eradication. Early laser photocoagulation has been advocated. We report a case of a middle aged man who presented with decreased vision and a sub retinal macular worm that required two laser sessions for complete eradication of the worm.

Choroidal metastases fundus autofluorescence imaging: correlation to clinical, OCT, and fluorescein angiographic findings.

BACKGROUND AND OBJECTIVE: To correlate fundus autofluorescence (FAF) characteristics of metastatic choroidal tumors with optical coherence tomography/scanning laser ophthalmoscope (OCT/SLO). PATIENTS AND METHODS: A retrospective review of 10 choroidal metastases in 9 patients. RESULTS: All tumors were amelanotic, although 8 exhibited surface pigmentation. FAF imaging revealed hyperautofluorescence in areas of focal pigmentation and subretinal fluid with hypoautofluorescent margins (n = 5) corresponding to OCT evidence of retinal pigment epithelial (RPE) thickening and subretinal fluid. Loss of RPE was FAF imaging hypoautofluorescent. FAF images changed with tumor growth. OCT best revealed elevation of the RPE and retina, RPE thickening and folds, and retinal detachment. CONCLUSION: FAF imaging best defined surface characteristics and tumor margins. FAF imaging hyperautofluorescence correlated to focal hyperpigmentation, subretinal fluid, and advancing tumor edges. OCT better demonstrated intraretinal findings (atrophy, subretinal fluid, and increased and lost RPE). This study shows that FAF imaging and OCT reveal unique tumor characteristics of choroidal metastasis.

Fundus Autofluorescence Imaging of Diffuse Uveal Melanocytic Proliferation.

Fundus autofluorescence imaging (FAF) in a case of diffuse uveal melanocytic proliferation is described in this study. It is a rare chorioretinopathy associated with systemic cancer, for which the exact pathological mechanisms are poorly understood. FAF-imaging revealed a diffuse background of hyper-autofluorescence associated with diffuse orange pigment deposition and islands of persistent hypo-fluorescence corresponding to loss of retinal pigment epithelium (RPE). In this disorder, increasingly smaller spots of FAF hypo-fluorescence were found from the center to the periphery of the affected retina. Fluorescein angiography demonstrated a negative of the FAF-images. FAF hypo-autofluorescence corresponded to optical coherence tomography (OCT) thinning or absence of the RPE-layer. Conversely, FAF hyper-autofluorescence correlated to thickening of the RPE-layer on OCT. The case demonstrates that FAF can be useful for the diagnosis of diffuse uveal melanocytic proliferation and offers greater insight into the pathophysiology of this disease.

Optical coherence tomography: pathology correlation of optic disc melanocytoma.

OBJECTIVE: To correlate combined optical coherence tomography (OCT) and scanning laser ophthalmoscope (SLO) imaging to clinical and histopathologic characteristics of optic disc melanocytoma (ODM). DESIGN: Retrospective, consecutive clinical case analysis. PARTICIPANTS: Twenty patients with ODM were evaluated. TESTING: All underwent ophthalmic examinations including a best-corrected visual acuity, slit-lamp examination, dilated ophthalmoscopy, fundus photography with angiography, B-scan ultrasonography, and combined OCT and SLO imaging. MAIN OUTCOME MEASURES: One eye, treated by enucleation, was evaluated by pathologic analysis and was correlated to its combined OCT and SLO images. These findings were correlated to clinical and OCT information from 19 patients with ODM. RESULTS: Histopathologic and combined OCT and SLO features included: disruption of the internal limiting membrane, disorganization of the retina (overlying the tumor), and visualization of the tumor's subretinal surface. Compressive and infiltrative changes in the optic nerve, peripapillary choroid, and retina were correlated directly to combined OCT and SLO images. To varying degrees, these histopathologic findings were seen on combined OCT and SLO. However, the pigment of the ODMs blocked OCT reflectance deep to the tumor's surface. CONCLUSIONS: This study demonstrated that OCT and SLO findings could be correlated directly with histopathologic characteristics. Imaging with OCT can be used to diagnose and correlate secondary retinal, superficial, and subretinal tumor characteristics. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The diagnostic value of exfoliative cytology vs histopathology for ocular surface squamous neoplasia.

PURPOSE: To determine the reliability and role of conjunctival exfoliative cytologic and histopathologic diagnosis of biopsied tissue in ocular surface squamous neoplasia. DESIGN: Retrospective review of an interventional case series of patients biopsied and treated for squamous conjunctival and corneal neoplasia. METHODS: Forty-nine patients who underwent conjunctival cytologic analysis (n = 36), conjunctival biopsy (n = 35), or both were evaluated. For the purposes of this study, three ocular pathologists reviewed the results of cytologic and biopsied tissue in a masked fashion. RESULTS: Evaluation of cytologic smears revealed a 91% concordance in interpretation of conjunctival cytologic material as no dysplasia vs dysplasia. The concordance dropped to 59% in grading the degree of dysplasia. The cytologic material was found to be inadequate for interpretation in 1 case. Evaluation of subsequent biopsy revealed a 98% concordance between the pathologists in interpretation of biopsied tissue as no dysplasia vs any degree of dysplasia. The concordance decreased to 83% in grading the degree of dysplasia. Cytologic evaluation was capable of distinguishing a neoplastic from nonneoplastic process before tissue biopsy in 80% of cases. CONCLUSIONS: Ocular surface cytologic analysis is a simple, safe, and relatively noninvasive diagnostic tool. It was found helpful in detecting dysplasia before surgical resection. It was used in the settings of recurrent tumor and for follow-up care of patients treated with topical chemotherapy. Although cytologic smears cannot replace incisional or excisional biopsy for definitive diagnosis, exfoliative cytologic analysis can play an important role in the diagnosis and management of patients with ocular surface squamous neoplasia.

Molecular-genetic analysis of two cases with retinoblastoma: benefits for disease management.

Effective counselling and management of retinoblastoma families using genetic information is presently practised in many parts of the world. We studied histopathological, chromosomal and molecular-genetic data of two retinoblastoma patients from India. The two patients, one with bilateral and the other with unilateral retinoblastoma, underwent complete ophthalmic examination, cytogenetic study, retinoblastoma gene (RB1) mutational analysis and RB1 promoter region methylation screening. In the bilateral retinoblastoma patient deletion of chromosome region 13q14 in peripheral blood lymphocytes and a hemizygous novel 8-bp deletion in exon 4 of RB1 in tumour sample were observed. In the unilaterally affected patient CGA to TGA transition protein truncation mutations were observed in exons 8 and 14 of RB1.