One-year results of intravitreal conbercept in treatment-naïve subjects with polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the functional and structural outcomes of intravitreal conbercept monotherapy using a "3 + pro re nata (PRN)" regimen in treatment-naïve subjects with polypoidal choroidal vasculopathy (PCV) up to 12 months. METHODS: Thirty subjects (30 eyes) with PCV participated in this interventional, retrospective study. All subjects received intravitreal injections of 0.5 mg (0.05 ml) conbercept using a "3 + PRN" regimen for 12 months. The changes in best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, polyp lesion area, and regression rate were evaluated at baseline, month 3, and month 12. RESULTS: At the study end-point, BCVA improved significantly from 52.80 ± 17.17 ETDRS letters at baseline to 62.20 ± 18.96 letters (P < 0.001), with a mean gain of 9.40 ± 14.97 letters. The central retinal thickness (CRT) significantly reduced from 454.93 ± 147.31 µm at baseline to 308.73 ± 106.80 µm (P < 0.001) at end-point, and the total macular volume (TMV) decreased from 9.51 ± 1.04 mm3 at baseline to 8.32 ± 0.84 mm3 at end-point (P < 0.001). The mean volume of pigment epithelial detachment (PED) decreased from 0.73 ± 0.97 mm3 at baseline to 0.48 ± 0.71 mm3 (P < 0.05) at month 3. At month 12, the mean volume of PED was 0.57 ± 0.80 mm3 (P > 0.05 compared to baseline). After the 3-monthly loading injections, 6 eyes (20.0%) showed complete polyp regression, whereas a total of 19 eyes (63.5%) showed complete regression at month 12. The average injections given per subject were 7.70 ± 1.81. CONCLUSION: Intravitreal conbercept using the "3 + PRN" regimen was effective in the treatment of PCV.

Autophagic Upregulation Is Cytoprotective in Ischemia/Reperfusion-Injured Retina and Retinal Progenitor Cells.

The cytoprotective versus cytotoxic role of macroautophagy in ocular ischemia/reperfusion injuries remains controversial and its effects under hyperglycemia are unclear. We investigated the involvement of autophagy in in vitro and in vivo normoglycemic and hyperglycemic models of retinal ischemia/reperfusion injury. Retinal ischemia (2 h) and reperfusion (2 or 22 h) was induced in wild-type and type I diabetic Ins2Akita/+ mice using a middle cerebral artery occlusion model. R28 retinal precursor cells were subjected to CoCl2-induced hypoxia with or without autophagic inhibitor NH4Cl. Autophagic regulation during ischemia/reperfusion was assessed through immunohistochemical detection and Western blotting of microtubule-associated protein 1A/1B-light chain 3 (LC3) and lysosomal associated membrane protein 1 (LAMP1). Effect of autophagic inhibition on cell viability and morphology under hypoxic conditions was also evaluated. Upregulation of autophagic markers in the inner retinae was seen after two hours reperfusion, with tapering of the response following 22 h of reperfusion in vivo. LC3-II turnover assays confirmed an increase in autophagic flux in our hypoxic in vitro model. Pharmacological autophagic inhibition under hypoxic conditions decreased cell survival and induced structural changes not demonstrated with autophagic inhibition alone. Yet no statistically significant different autophagic responses in ischemia/reperfusion injuries were seen between the two glycemic states.

Sociodemographic, behavioral, and medical risk factors associated with visual impairment among older adults: a community-based pilot survey in Southern District of Hong Kong.

BACKGROUND: The last visual survey of older adults in Hong Kong was a district-level study in 2002, with no assessment of behavioral and medical risk factors for visual impairment (VI). Our objectives were to determine the latest VI prevalence among older adults, significance of any spatial and temporal differences on the prevalence, and any associations of sociodemographic, behavioral and medical risk factors with VI from a multi-perspective analysis. METHODS: Community-based pilot survey of residents from a suburb of Hong Kong, aged ≥50, using a standardized questionnaire, was conducted in 2016. RESULTS: Of the 222 subjects, crude rates of bilateral and unilateral VI were 9.46 and 32.88%, respectively, or corresponding age-and-gender-adjusted rates of 6.89 and 30.5%. Older age and lower educational were associated with higher risk for unilateral VI, while older age, temporary housing, obesity and hyperlipidemia were associated with higher risk for bilateral VI. Smoking and alcohol-drinking status were not associated with unilateral or bilateral VI. Relative changes in ORs of hypertension or educational level on unilateral or bilateral VI were >  10% after adjusting for age. Interaction term between hyperlipidemia and gender or obesity was significant for unilateral VI. Gender, hypertension and cataract were not associated with unilateral or bilateral VI in general population of pooled analysis but were identified as risk factors in specific subgroups of stratified analysis. Refractive error (myopia or hyperopia) was significantly associated with VI in the eye-level analysis after adjusting the inter-eye correlation. CONCLUSIONS: Sociodemographic and medical risk factors contributed to VI, but behavioral risk factors did not. Sociodemographic disparities of visual health existed. Age was the confounders of the VI-hypertension or VI-educational level relationships. Gender and obesity were more likely to have multiplicative effect on unilateral VI when combined with hyperlipidemia. Stratified analysis should be conducted to provide further insight into the risk factors for VI in specific populations. Uncorrected refractive error remains a significant cause of impaired vision. The spatial and temporal differences in bilateral VI prevalence from the previous local study indicates a territory-wide survey is needed to assess regional differences and overall prevalence of VI in Hong Kong.

Single-Session High-Intensity Focused Ultrasound Treatment for Persistent or Relapsed Graves Disease: Preliminary Experience in a Prospective Study.

Purpose To evaluate the safety and efficacy of ultrasonography (US)-guided high-intensity focused ultrasound (HIFU) ablation as a treatment for medically refractory Graves disease (GD). Materials and Methods After ethics approval, a prospective trial (NCT02685514) was performed from November 2015 to February 2016. Thirty patients underwent ablation of the entire right and left thyroid lobes, with areas near the tracheal-esophageal groove and common carotid artery left unablated. Serum thyroid-stimulating hormone (TSH), free T4 (FT4), antithyroid autoantibodies, and TSH receptor (TSHR) antibody levels were evaluated afterward, and US color Doppler, US volumetry, and eye assessment were performed. The primary outcome was the 12-month relapse rate. Relapse referred to hyperthyroidism (FT4 > 23 pmol/L) afterward. Variables associated with relapse were analyzed by using binary logistic regression. Results The technical success rate was 96.7%. The cohort comprised entirely women, with a median age of 38.2 years (interquartile range, 29.5-49.0 years). After 12 months, eight patients (26.7%; 95% confidence interval [CI]: 14.19%, 44.95%) experienced relapse. One patient (3.3%; 95% CI: 0.59%, 16.67%) experienced vocal cord palsy, while two patients (6.7%; 95% CI: 1.85%, 21.33%) experienced Horner syndrome, but none of these conditions were permanent. No changes in gland volume, antithyroid autoantibody levels, and ophthalmic parameters were found at 12-month follow-up. Baseline TSHR was found to have decreased significantly at 6- and 12-month follow-up (P < .001 for both). TSHR antibody (odds ratio [OR] = 1.414; 95% CI: 1.018, 1.965; P = .039) and gland volume (OR = 0.557; 95% CI: 0.353, 0.880; P = .012) were associated with 12-month relapse, with higher antibody levels conferring a higher likelihood and smaller gland volumes conferring a lower likelihood. Conclusion US-guided HIFU of the thyroid may be a safe and efficacious treatment in patients with persistent or relapsed GD. However, further study is warranted before it can become mainstream for this indication. © RSNA, 2017 Online supplemental material is available for this article.

Contribution of systemic factors on macular vessel density: a sex-specific population-based study.

PURPOSE: To evaluate the influence of systemic factors on macular vessel density in quantitative Optical Coherence Tomography Angiography (OCTA) by sex. STUDY DESIGN: A cross-sectional study. METHODS: A total of 2018 adults were recruited in this study. Participants were excluded (n=964) due to missing data, eye-related problems, or low OCTA scan quality. Macular vessel densities were measured with OCTA using split-spectrum amplitude decorrelation angiography algorithm. Only the data from the right eyes were selected for analysis. Multivariable linear regression analysis was performed to determine the associations between macular vessel density and obesity-related systemic factors in each gender group. RESULTS: The right eyes of 1054 participants (59.6% women) were enrolled. Men had significantly higher obesity parameters and associated risk factors. In multivariable linear regression analysis in men, older age and type 2 diabetes mellitus were independently associated with lower superficial retinal vessel density (ß = -0.37, p = 0.002; ß = -1.22, p = 0.03) and deep retinal vessel density, respectively (ß = -0.66, p < 0.001; ß = -1.76, p = 0.02); positive association was also observed between body mass index (BMI) and superficial retinal vessel density (ß = 0.56, p = 0.02). In women, only higher systolic blood pressure was independently associated with a lower deep retinal vessel density (ß = -0.50, p = 0.003). CONCLUSIONS: This large cross-sectional study shows that older age and type 2 diabetes mellitus are associated with lower superficial and deep retinal capillary vessel density in men. This may help clinicians better understand how systemic factors influence retinal vessel density in different genders and future studies can ascertain more potential sex differences.

Circulating AFABP, FGF21, and PEDF Levels as Prognostic Biomarkers of Sight-threatening Diabetic Retinopathy.

CONTEXT: Adipocyte fatty acid-binding protein (AFABP), fibroblast growth factor 21 (FGF21), and pigment epithelium-derived factor (PEDF) are 3 diabetes-related biomarkers whose circulating levels had been shown to associate with nephropathy progression in Chinese patients with type 2 diabetes. OBJECTIVE: Here, we evaluated and compared their prospective associations with the development of sight-threatening DR (STDR), another important diabetic microvascular complication. METHODS: Baseline serum AFABP, PEDF, and FGF21 levels were measured in 4760 Chinese individuals with type 2 diabetes and without STDR at baseline. The associations of these biomarkers with incident STDR were analyzed using Cox regression analysis. RESULTS: Among these 4760 participants (mean diabetes duration of 11 years and ≥ 50% with nonproliferative DR at baseline), 172 participants developed STDR over a median follow-up of 8.8 years. Participants with incident STDR had comparable baseline serum FGF21 levels but significantly higher baseline serum AFABP and PEDF levels (both P < .001) than those without. However, in multivariable Cox regression analysis, only serum AFABP remained independently associated with incident STDR (hazard ratio 1.28; 95% CI, 1.05-1.55; P = .013). The addition of serum AFABP to a clinical model of conventional STDR risk factors including diabetes duration, glycemic control, albuminuria, and baseline DR status significantly improved the c statistics (P < .001), net reclassification index (P = .0027), and integrated discrimination index (P = .033) in predicting incident STDR among participants without DR or with mild DR at baseline. CONCLUSION: Among the 3 diabetes-related biomarkers, serum AFABP level appeared to be a more clinically useful biomarker for predicting incident STDR in type 2 diabetes.

Promises of stem cell therapy for retinal degenerative diseases.

With the development of stem cell technology, stem cell-based therapy for retinal degeneration has been proposed to restore the visual function. Many animal studies and some clinical trials have shown encouraging results of stem cell-based therapy in retinal degenerative diseases. While stem cell-based therapy is a promising strategy to replace damaged retinal cells and ultimately cure retinal degeneration, there are several important challenges which need to be overcome before stem cell technology can be applied widely in clinical settings. In this review, different types of donor cell origins used in retinal treatments, potential target cell types for therapy, methods of stem cell delivery to the eye, assessments of potential risks in stem cell therapy, as well as future developments of retinal stem cells therapy, will be discussed.

Prevention of age-related macular degeneration.

Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula.

Prevalence and associations of myopia in Hong Kong primary school students.

PURPOSE: To examine the prevalence of myopia in primary school children in Hong Kong, and the risk factors for myopia development. STUDY DESIGN: A cross-sectional study. METHODS: Subjective refraction and axial length were measured in all participants. Structured questionnaire was completed by the parents to assess risk factors of myopia. RESULTS: A total of 1396 children (491 boys) from Grade 1 to Grade 6 from 4 primary schools in Sham Shui Po district of Hong Kong participated. All participants underwent non-cycloplegic refraction. The overall prevalence of myopia (spherical equivalent, SE ≤ -0.5 diopter [D]) was 37.7%, which significantly increased with age, from 13.3% at grade 1 to 54.7% at grade 6. The prevalence of moderate myopia (-3.0D < SE < -6.0D) increased from 1.6% at grade 1 to 18.2% at grade 6 and the prevalence of high myopia (SE < = -6.0 D and/or AL ≥ 26.5 mm) increased from 0.94% (7/747) in grade 1-3 students to 1.85% (12/649) in grade 4-6 students. Among the students with myopia, only 23.6% of the parents knew their children had refractive errors and only 19.8% of the children wore glasses. Multivariate logistic regression analysis showed myopia development was significantly associated with older age (OR = 1.36, P = 0.008), better academic ranking in class in the preceding semester (OR = 1.01, P = 0.02) and absence of routine eye check (OR = 2.70, P = 0.001). CONCLUSION: The prevalence of myopia in primary school students in Hong Kong is high. There is a low level of awareness of refractive errors among parents, and high proportion of under-correction, resulting in suboptimal vision.

Saving sight in China and beyond: the Lifeline Express model.

Cataract and diabetic retinopathy are leading causes of blindness globally. Lifeline Express (LEX) has pioneered the provision of cataract surgery in rural China from custom-built trains and eye centres nationwide. Over the past two decades, LEX has provided free cataract surgery for over 180 000 patients in China. In China, half of the adult population has prediabetes and 113 million adults have diabetes. Recognising the rising threat of diabetic retinopathy, LEX has expanded to providing free diabetic retinopathy screening nationwide by establishing 29 Diabetic Retinopathy Screening Centres across China. Source of referrals included host hospitals, the community and out-reach mobile vans equipped with fundus cameras. Fundi photos taken in the mobile vans were electronically transferred to primary graders. LEX also leveraged the widespread smartphone use to provide electronic medical reports via WeChat, the most popular instant messenger app in China. From April 2014 to December 2016, 34 506 patients with diabetes underwent screening, of which 27.2% (9,396) were identified to have diabetic retinopathy. China's latest national health strategy ('Healthy China 2030 Plan') has championed the 'prevention first' principle and early screening of chronic diseases. LEX has accordingly evolved to extend its services to save sight in China-from cataract surgery to diabetic retinopathy screening and most recently outreaching beyond its national borders in a pilot South-South collaboration. With health at the top of the China's developmental agenda and the country's growing role in global health-LEX's large-scale telemedicine-enabled programme could represent a potentially scalable model for nationwide diabetic retinopathy screening elsewhere.

Transcorneal Electrical Stimulation Inhibits Retinal Microglial Activation and Enhances Retinal Ganglion Cell Survival After Acute Ocular Hypertensive Injury.

PURPOSE: To investigate the effect of transcorneal electrical stimulation (TcES) on retinal ganglion cell (RGC) function and survival after acute ocular hypertension-related retinal injury in gerbil eyes. METHODS: Gerbil eyes were subjected to acute ocular hypertensive injury (80 mm Hg for 60 minutes). In the treatment group, TcES was applied to the surgical eye immediately and then twice weekly for a total of 1 month. In the control group, sham TcES was given to the surgical eye at the same time points. Retinal function was assessed and compared between groups using flash electroretinography. For histological analysis, the number of RGC and microglial cells were counted by immunofluorescence staining after the gerbils were sacrificed on day 7 and day 28. Real-time polymerase chain reaction and western blot analysis were conducted to compare expression of interleukin (IL)-10, IL-6, COX-2, tumor necrosis factor (TNF)-α, and NF-κB phosphorylation among groups. RESULTS: TcES-treated eyes had significantly higher RGC survival at 1 month compared to controls. This was associated with RGC function. Furthermore, TcES-treated eyes were shown to have increased IL-10 expression, with a corresponding reduction in IL-6 and COX-2 expression as well as reduction in NF-κB phosphorylation. This was associated with a suppression in microglial cell activation in TcES-treated eyes. CONCLUSIONS: Early treatment with TcES in gerbils protected the RGC from secondary damage and preserved retinal function in acute ocular hypertensive injury through modulation of the microglial-cell activated local inflammatory response. TRANSLATIONAL RELEVANCE: Our study strengthens the argument for translating TcES as a viable treatment in acute glaucoma.

Choroidal microvascular proliferation secondary to diabetes mellitus.

Diabetes is a common endocrine disorder associated with peripheral microvascular diseases such as proliferative retinal microangiopathy (or diabetic retinopathy), which may lead to blindness. Unfortunately, diabetic microvascular abnormalities in the choroid are underestimated in clinical practice. Recent literature has revealed that the severity of diabetic retinopathy is aggravated by choroidopathy resulting from hyperglycemia. Here, we introduce a case of diabetic retinopathy with choroidal neovascularization membrane but without signs of retinal microvascular proliferation or drusen. We investigated the pathogenesis of choroidal microvascular proliferation secondary to diabetes. We postulate that choroidal neovascularization is an intraocular microvascular complication of diabetes mellitus. Intravitreal anti-vascular endothelial growth factor therapy may be a treatment option for microvascular proliferation in both retina and choroids.

Use of anti-vascular endothelial growth factor in the management of pterygium.

The rising success of anti-vascular endothelial growth factor (VEGF) therapies in ocular disease has stimulated the use of such treatments in the surgical management of pterygium. We reviewed the literature to better understand the safety and efficacy of the adjunctive role of anti-VEGF treatments for pterygium excision. Without surgery, anti-VEGF alone may favourably alter symptoms and vascularity, but does not cause pterygium regression. Some evidence supports the use of anti-VEGF as an adjuvant therapy to surgery, especially when using a higher dose and a more frequent dosing regimen. Overall, anti-VEGF is generally safe and well tolerated in patients with pterygium. Currently, the evidence does not conclusively support the use of anti-VEGF in pterygium surgery. However, further research may guide unanswered questions regarding the interaction between VEGF and other factors responsible for pterygium growth. In addition, the optimal route and dosage of anti-VEGF administration is not yet known.

Predisposing Factors, Microbial Characteristics, and Clinical Outcome of Microbial Keratitis in a Tertiary Centre in Hong Kong: A 10-Year Experience.

Purpose. To study the risk factors, microbial profile, antibiotic susceptibility pattern, and outcome for microbial keratitis over the past 10 years in a tertiary center in Hong Kong. Methods. All cases with corneal scraping performed in Queen Mary Hospital, Hong Kong from January 2004 to December 2013 were included. Clinical outcome was defined as poor if the final visual acuity (VA) was abnormal or worse than presenting VA, a major complication occurred, or therapeutic keratoplasty was required. Results. 347 scrapes were performed in the 10-year period growing 130 microorganisms (32.3% culture positive rate). Contact lens use was the commonest risk factor. The commonest isolates were coagulase-negative Staphylococcus and Pseudomonas aeruginosa. Fluoroquinolone susceptibility was tested in 47 Gram-negative bacteria with 93.6% susceptibility (100% for Pseudomonas). 90.7% of cases had good visual outcome. Multivariate logistic regression showed age (p = 0.03), trauma (p = 0.006), and ulcer size >3 mm (p = 0.039) to be independently associated with poor outcome. Conclusion. There was no shifting trend in the isolate distribution or emergence of resistant strains in our study. Contact lens wear was the commonest risk factor, with Pseudomonas being the most frequent isolate in this group. It remained 100% susceptible to fluoroquinolones and 97% cases had good visual outcome.

Congenital glaucoma from Sturge-Weber syndrome: a modified surgical approach.

Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder that causes congenital glaucoma. Previous experiences have shown that drainage procedures are often required to control associated glaucoma. The conventional surgical approach in trabeculectomy carries a significant risk of intraoperative expulsive hemorrhage. Here, we describe a modified approach of the conventional trabeculectomy technique, which may lower the risk of expulsive hemorrhage. A viscoelastic device was employed to maintain a steady intraocular pressure throughout the procedure. Details of the surgical technique and material used are described. One patient with congenital glaucoma associated with SWS underwent a successful trabeculectomy using the modified technique. Postoperative intraocular pressure was successfully reduced and no intraoperative complications occurred. We describe a successful case of trabeculectomy in a SWS case where a modified technique was applied.