Bevacizumab (Avastin) for the treatment of ocular disease.

Multiple early gastric cancers (EGCs) may develop in 6–14% of patients even after achieving curative endoscopic submucosal dissection (ESD); however, a useful biomarker for predicting recurrence is not available. The present study investigated whether the expression of CD44 variant 9 (CD44v9), a functional cancer stem cell marker, in the primary gastric cancer tissue represents an indicator of recurrence. Eighty-eight patients who underwent ESD for EGC from 2008 to 2010 were enrolled and monitored for recurrence for 3 years. The expression levels of CD44v9 in the tissue of initial EGCs were evaluated by immunohistochemistry, and the recurrence rate was compared between CD44v9-positive and CD44v9-negative groups. The mucin phenotype and expression of microRNA-21 (miR-21) and programmed cell death protein 4 (PDCD4) were also analysed. The recurrence rate of EGC was significantly higher in the CD44v9-positive group than in the CD44v9-negative group (hazard ratio (HR), 21.8; 95% confidence interval (CI), 5.71–83.1). However, mucin phenotypes and the expression of miR-21 and PDCD4 did not predict recurrence after ESD. Meanwhile, grade of gastric atrophy was also identified as a significant marker of multiple recurrence (HR, 4.95; 95% CI, 1.30–18.8). CD44 variant 9 expression represents a potential predictive marker for recurrence in EGC.

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CD44 variant 9 expression in primary early gastric cancer as a predictive marker for recurrence

Current management of Coats disease.

Aim To evaluate the effect of supplemental intravitreal bevacizumab for management of Coats9 disease. Methods Retrospective analysis of eight patients with Coats9 disease manifesting total or partial exudative retinal detachment where the retinal telangiectasia was treated with standard laser photocoagulation and/or cryotherapy plus additional intravitreal bevacizumab (1.25 mg/0.05 ml). Results The mean patient age was 88 (range 7–240) months and 63% were male. Coats9 disease was classified as stage 2 (n=1, 12%), 3a (n=3, 38%) and 3b (n=4, 50%). Features included retinal detachment (n=8, 100% with mean detachment extent involving 8 clock hours), telangiectasia (n=8, 100% with mean extent of 8 clock hours), peripheral retinal ischaemia on fluorescein angiography (n=7, 88%) and no evidence of neovascularisation. Treatment consisted of cryotherapy (n=8, 100%), laser photocoagulation (n=4, 50%) and bevacizumab intravitreal injection (n=8) with median number of one injection per eye (mean 1.75, and range 1–4 injections). After a mean follow-up of 8.5 months, resolution of retinopathy (n=8, 100%), Coats9-related subretinal fluid (n=8, 100%) and retinal exudation (n=6, 75%) was noted. However, vitreous fibrosis developed (n=4, 50%) at a mean of 5 months following a mean of 1.75 bevacizumab injections with three (38%) evolving into traction retinal detachment. Conclusion Coats9 disease treated with intravitreal bevacizumab in addition to standard therapy can develop to vitreoretinal fibrosis and potentially traction retinal detachment. These tractional features are not often found in Coats9 disease treated with standard measures without bevacizumab. Caution is advised in the use of bevacizumab for patients with Coats9 disease.

https://bjo.bmj.com/content/bjophthalmol/96/3/356.full.pdf

Bevacizumab for Coats' disease with exudative retinal detachment and risk of vitreoretinal traction

To compare intraocular vascular endothelial growth factor (VEGF) level in patients with and without Coats’ disease, and to report a case of Coats’ disease that responded to intravitreal injection of bevacizumab. Intraocular fluid was obtained from four eyes with Coats’ disease (subretinal fluid in three eyes and aqueous in one eye) and from five eyes with rhegmatogenous retinal detachment (subretinal fluid in four eyes and vitreous in one eye). Intraocular VEGF level was compared between these two groups. In one eye with stage 2B Coats’ disease, macular edema, visual acuity, and intraocular VEGF level were compared before and after intravitreal injection of bevacizumab. Mean intraocular VEGF level in eyes with Coats’ disease was 2,394.5 pg/ml, compared to 15.3 pg/ml in eyes with rhegmagenous retinal detachment. In the eye with stage 2B Coats’ disease, macular edema was reduced after bevacizumab injection, and the visual acuity improved from 0.05 to 0.2. Intraocular VEGF level decreased from 1247 pg/ml to 20.4 pg/ml 1 month after the injection. Coats’ disease is associated with increased intraocular VEGF level. Bevacizumab may be a valuable adjunctive treatment for Coats’ disease.

Elevated vascular endothelial growth factor level in Coats' disease and possible therapeutic role of bevacizumab

We describe the role of intravitreal anti-vascular endothelial growth factor (VEGF) agents in Coats' disease in children. In a prospective, interventional, non-randomized case series, three patients (three eyes) aged 16, seven and two years were diagnosed to have Coats' disease. In Case 1 (16 yr/ male) with macular edema, previous laser photocoagulation being unsuccessful, intravitreal pegaptanib sodium (Macugen™) was tried. Case 2 (seven yr/ male) and Case 3 (two yr/ female) were diagnosed to have Stage 4 Coats' and underwent external needle drainage, laser photocoagulation, SF6 gas injection and intravitreal injection of bevacizumab (Avastin™). Reduction of exudation and attached posterior pole (Cases 2 and 3) was seen at a follow-up of six months and two months respectively. Intravitreal anti-VEGF agents may be successfully used as adjunct treatment in select cases of Coats' disease in childhood.

Intravitreal anti-vascular endothelial growth factor agents as an adjunct in the management of Coats' disease in children.

Aim: To describe the clinical features, treatment and outcome patterns in 307 eyes with Coats' disease. Materials and Methods: Retrospective chart review of patients diagnosed with Coats' disease between January 1996 and January 2006 from a single referral center in southern India. Results: Two hundred and eighty patients (307 eyes) with mean age of 15.67 years (range: Four months-80 years) were included. Decreased vision (77%), unilateral affection (90%) and male preponderance (83.4%) were chief presenting features. Anterior segment involvement was seen in 67 (21.8%) eyes. Retinal telangiectasia were seen in 302 (99%) eyes, exudation in 274 (89%) eyes and retinal detachment in 158 (51.5%) eyes. Four-quadrant disease was seen in 207 (67.2 %) eyes. Visual acuity was < 20/200 in 249 (80.9%) eyes. One hundred and nine of 176 treated eyes (61.93%) had favorable anatomical outcome; 207 of 280 eyes (74%) had an optimal structural outcome. Seventeen (5.3%) eyes were enucleated. Complications following treatment included phthisis bulbi (7%), neovascular glaucoma (5%), epiretinal membrane (4.4%) and rubeosis iridis (4.4%). Conclusion: Indian patients with Coats' disease have a high male predominance, the majority of whom present with severe visual impairment and extensive four-quadrant exudation. Unusual presentations such as pain, vitreous hemorrhage and a high incidence of anterior segment involvement are distinctive to Indian eyes.

Coats' disease: An Indian perspective

Letter to the EditorAutofluorescence Imaging

Background: Coats' disease diagnosed in adulthood is an idiopathic, retinal exudative vascular disease without an inciting factor and has retinal features different from the childhood disease. Aim: To describe clinical features, treatment, and outcomes of eyes with Coats' disease first diagnosed in patients 35 years or older. Materials and Methods: Retrospective chart review of patients first diagnosed with Coats' disease at the age of 35 years or more at a tertiary eye care center between January 1995 and 2012. Eyes with retinal exudation or Coats'-like response from secondary causes were excluded. Results: Forty-five of 646 patients (7%) diagnosed with Coats' disease had adult-onset disease. Mean age at presentation was 47 years. Systemic hypertension was the most common (22%) systemic association and decreased vision the predominant presenting feature (83%). Localized (<6 clock h) presentation (74%) was unique to adults as against diffuse involvement (69%) in children (P < 0.001). Eyes were treated with laser photocoagulation 29 (60%), cryotherapy (4%), or both (2%) with surgical intervention in three (6%) eyes. Following treatment eight (35%) eyes improved, 11 (48%) eyes were stable while four (12%) eyes worsened due to complications. Conclusion: Adult-onset Coats' disease has less extensive involvement, more benign natural course, and a more favorable treatment outcome as against the childhood-onset disease. The bilateral presentation emphasizes the need for regular follow-up to detect possible future involvement of the fellow eye.

Coats’ disease of adult-onset in 48 eyes

The purpose of this study was to compare the structural outcome of laser treatment to avascular retina and ridge versus laser treatment to avascular retina alone in cases with threshold retinopathy of prematurity (ROP). A prospective, randomized, interventional, comparative study of consecutive cases referred to a single tertiary center was considered here. 50 infants with bilateral symmetrical threshold ROP were recruited into this study over a period of 3 years. Threshold ROP was defined as per CRYO-ROP study. Perinatal history details for all patients including significant maternal history were recorded. One eye of each patient was randomized (Microsoft Excel 2000) to one of the two treatment groups—laser treatment to avascular retina (Group A) or laser treatment to avascular retina and ridge (Group B). Laser treatment was performed with a 810 nm diode laser (Iris Medical Instruments, Inc. Mountain View, CA, USA). Treatment was continued until regression of ROP. Structural outcome was assessed at a minimum follow-up of 6 months and was considered favorable or unfavorable as per the CRYO-ROP study criteria. An unfavorable outcome consisted of either (1) a retinal fold involving the macula; (2) any retinal detachment involving zone 1; or (3) a retrolental mass that obscured visualization of the posterior pole. Secondary outcome measures included the difference in time to regression of ROP and complications of treatment between the two treatment groups. 100 eyes of 50 infants received laser photocoagulation for threshold ROP after randomization (50 eyes in each group). Of these 50 infants, 20 (40%) were female and 30 (60%) were male. A significant proportion of the children (46%) were conceived as twins. The average birth weight was 1360 ± 326 g (range 750−2200 g). The mean gestational age at birth was 30.72 ± 1.6 weeks (range 26−36 weeks). Zone I disease was present in 14 (14%) eyes and zone II in the remaining 86 eyes (86%). Threshold stage retinopathy (CRYO-ROP criteria) extending 360° (12 clock hours) was present in 21 infants (42%), 5 contiguous clock hours of stage 3+ in 14 infants (28%) and intermediate range in the remaining 15 infants (30%). At 6 months follow-up, 3 eyes (6%) in group A and 1 eye (2%) in group B had an adverse structural outcome; however, the time to regression of retinopathy 2.98 ± 1.5 weeks in group A and 3.12 ± 1.1 in group B (P = 0.889) and the rate of complications such as retinal hemorrhage, 3 eyes in group A and 4 eyes in group B, was comparable. Zone I eyes showed equal incidence of favorable anatomical outcome (85.7%) in each group. Laser treatment to ridge was found to be safe and effective in the treatment of threshold ROP in this short-term pilot study; however, it needs to be ascertained whether this treatment has long-term advantages over conventional laser treatment to avascular retina, as well as the long-term benefits of treatment to ridge.

Laser photocoagulation (810 nm diode) for threshold retinopathy of prematurity: a prospective randomized pilot study of treatment to ridge and avascular retina versus avascular retina alone

Mahesh Uparkar

Papers

Intravitreal anti-vascular endothelial growth factor agents as an adjunct in the management of Coats' disease in children.

Coats' disease: An Indian perspective

Letter to the EditorAutofluorescence Imaging

Coats’ disease of adult-onset in 48 eyes

Laser photocoagulation (810 nm diode) for threshold retinopathy of prematurity: a prospective randomized pilot study of treatment to ridge and avascular retina versus avascular retina alone