Peter Cackett

Polypoidal choroidal vasculopathy and neovascular age-related macular degeneration: Same or different disease?

Neovascular age-related macular degeneration (nAMD) is the commonest cause of severe visual impairment in older adults in Caucasian white populations. Polypoidal choroidal vasculopathy (PCV) has been described as a separate clinical entity differing from nAMD and other macular diseases associated with subretinal neovascularization. It remains controversial as to whether or not PCV represents a sub-type of nAMD. This article summarizes the current literature on the clinical, pathophysiological and epidemiological features and treatment responses of PCV and compares this condition to nAMD. Patients with PCV are younger and more likely Asians, and eyes with PCV lack drusen, often present with serosanguinous maculopathy or hemorrhagic pigment epithelial detachment, and have differing responses to photodynamic therapy and anti-vascular endothelial growth factor (VEGF) agents. There are also significant differences in angiographic and optical coherence tomography features between PCV and nAMD. Histopathological studies suggest differences in the anatomical details of the associated vascular abnormalities in the retina and choroids and the relative role of VEGF. There is emerging evidence of common molecular genetic determinants involving complement pathway and common environmental risk factors (e.g. smoking). Such information could further assist clinicians involved in the care of elderly patients with these conditions.

Smoking, Cardiovascular Risk Factors, and Age-related Macular Degeneration in Asians: The Singapore Malay Eye Study

PURPOSE To assess associations between smoking and cardiovascular risk factors and prevalent age-related macular degeneration (AMD) in the Singapore Malay population. DESIGN Population-based, cross-sectional study. METHODS A total of 3,280 Malay adults age 40 to 80 years were included in the study. Early and late AMD signs were graded from retinal photographs following Wisconsin system. All participants had interview, systemic examination, and laboratory investigations to determine smoking status and cardiovascular risk factors. RESULTS A total of 3,265 participants had gradable photos, 21 (0.6%) with late AMD and 169 (5.2%) with early AMD. After adjusting for age and gender, current smokers were significantly more likely to have late AMD (odds ratio [OR], 3.79; 95% confidence interval [CI], 1.40 to 10.23). This association was stronger among those who currently smoked >5 packs of cigarettes per week (OR, 9.35; 95% CI, 2.49 to 35.08). CONCLUSIONS Smoking was associated with a higher late AMD prevalence in Malays, consistent with findings from studies in White populations.

A classification system for polypoidal choroidal vasculopathy.

Purpose: To describe the demographic features and clinical characteristics of polypoidal choroidal vasculopathy (PCV) in Chinese patients and define a new classification system. Methods: Retrospective review of 138 eyes of 123 patients presenting to the Singapore National Eye Center with PCV. Patients underwent ophthalmologic examination including digital color fundus photography and stereoscopic indocyanine green angiography. Classification based on indocyanine green angiography findings. Results: Mean age of patient 68.3 years and 62.4% were men. PCV was unilateral in 87.8% cases and age-related maculopathy was present in the unaffected fellow eye in 22.8%. Average largest size of polyp was 207 &mgr;m. PCV lesions were found in multiple discrete areas in 34.8%. Formation of lesion was cluster in 66.7%, single in 27.5%, and string in 5.8%. PCV lesions were found in the extrafoveal area in 63.0%, subfoveal in 29.7%, juxtafoveal in 15.9%, and peripapillary in 8.0%. Conclusions: Demographics of PCV, unilaterality and frequency of age-related maculopathy in fellow eye similar to other reports in Asians. We describe a classification system for PCV comprising polyp size, location, formation, and number of discrete polyp areas, which can be used for prospective interventional clinical studies and may aid in future prognosis and management of this condition.

Relationship of smoking and cardiovascular risk factors with polypoidal choroidal vasculopathy and age-related macular degeneration in Chinese persons.

PURPOSE Polypoidal choroidal vasculopathy (PCV) has been described as a distinct clinical entity from choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The present study aimed to determine risk factors for PCV and to compare associations with those for CNV secondary to AMD. DESIGN Case-control study. PARTICIPANTS Patients of Chinese ethnicity with clinically and angiographically diagnosed PCV (n = 123) or CNV secondary to AMD (n = 128) were recruited from a tertiary eye hospital in Singapore. Controls without signs of PCV, CNV secondary to AMD, or other retinal pathologic features (n = 1489) were selected from a population-based study. METHODS Patients underwent an ophthalmologic examination including digital color fundus photography, stereoscopic fluorescein angiography (FA), and indocyanine green angiography (ICGA). Classification into PCV or CNV secondary to AMD was based on FA and ICGA findings. Risk factors were determined from a standardized interview, with blood pressure recorded using a digital automatic blood pressure monitor. MAIN OUTCOME MEASURES Polypoidal choroidal vasculopathy or CNV secondary to AMD. RESULTS Persons who smoked were more likely to have PCV (39.9% vs. 13.4%) or CNV secondary to AMD (45.0% vs. 12.3%) than those who did not smoke. After controlling for age, gender, diabetes, hypercholesterolemia, and hypertension, persons who smoked were 4 times more likely to have PCV (odds ratio [OR], 4.4; 95% confidence interval [CI], 2.5-7.7; P<0.001) and CNV secondary to AMD (OR, 4.9; 95% CI, 2.7-8.8; P<0.001). A significant, negative association also was found between diastolic blood pressure and CNV secondary to AMD (OR, 0.7; 95% CI, 0.5-0.9; P = 0.017, adjusted for age, gender, smoking, diabetes, and hypercholesterolemia), but diastolic blood pressure was not associated with PCV. CONCLUSIONS Smoking but not other vascular risk factors is significantly associated with both PCV and CNV secondary to AMD in Chinese persons. The similarity of associations suggests that there may be common risk factors and pathological mechanisms.

Education, socio-economic status and age-related macular degeneration in Asians: the Singapore Malay Eye Study

Background/aims: Low socio-economic status is increasingly being identified as a risk marker for chronic diseases, but few studies have investigated the link between socio-economic factors and age-related macular degeneration (AMD). The present study aimed to assess the association between socio-economic status and the prevalence of AMD. Methods: A population-based cross-sectional study of 3280 (78.7% response rate) Malay adults aged 40–80 years residing in 15 south-western districts of Singapore. AMD was graded from retinal photographs at a central reading centre using the modified Wisconsin AMD scale. Early and late AMD signs were graded from retinal photographs following the Wisconsin grading system. Socio-economic status including education, housing type and income were determined from a detailed interview. Results: Of the participants, 3265 had photographs of sufficient quality for grading of AMD. Early AMD was present in 168 (5.1%) and late AMD in 21 (0.6%). After adjusting for age, gender, smoking, hypertension, diabetes and body mass index, participants with lower educational levels were significantly more likely to have early AMD (multivariate OR 2.2, 95% CI 1.2 to 4.0). This association was stronger in persons who had never smoked (multivariate OR 3.6, 95% confidence CI 1.4 to 9.4). However, no association with housing type or income was seen. Conclusions: Low educational level is associated with a higher prevalence of early AMD signs in our Asian population, independent of age, cardiovascular risk factors and cigarette smoking.

Nystagmus secondary to drug exposure in utero.

Aim: To report the occurrence of nystagmus in children exposed to opiates and/or benzodiazepines during pregnancy, and to describe the associated ocular and systemic findings. Methods: Clinical examination and casenote review of 14 children with nystagmus whose mothers had misused opiates and/or benzodiazepines during pregnancy. Results: Twelve children were exposed to opiates during pregnancy, of whom nine had also been exposed to benzodiazepines. Two children were exposed to benzodiazepines alone. In the primary position, the nystagmus was a fine horizontal pendular type in 10 (71.4%) children and was a fine horizontal jerk nystagmus in the other 4 (28.6%) children. The onset of the nystagmus probably occurred in the first 6 months of life in all cases. The mean binocular best-corrected logarithm of the minimum angle of resolution visual acuity was 0.59 (20/80). Electroretinogram and visual evoked potential examinations were found to be normal in the three children tested. Nine (64.3%) children had developmental delay and at least 7 (50%) had delayed visual maturation. Six children had microcephaly and two had bilateral optic nerve hypoplasia. None of the children had a specific neurological diagnosis or seizure disorder. Conclusion: This study strongly supports a teratogenic association between exposure to controlled drugs in utero and infantile nystagmus. Furthermore, the nystagmus and associated clinical features seem to be particularly associated with combined use of opiates and benzodiazepines. Exposure to opiates and/or benzodiazepines during pregnancy should be considered in the differential diagnosis of infantile nystagmus.

Combined intravitreal bevacizumab and argon laser treatment for Coats’ disease

Editor, C oats’ disease is characterized by the formation of telangiectatic and aneurysmal changes of the retinal vessels and is associated with a large amount of yellowish subretinal exudates (Harris 1970). Previous treatment options have included cryotherapy and laser photocoagulation of telangiectasia and aneurysms, surgery for exudative retinal detachment and enucleation (reserved for those with intractable rubeotic glaucoma) (Kiratli & Eldem 1998). We report a case of Coats’ disease that was treated successfully with a combination of bevacizumab and laser photocoagulation. A 15-year-old Chinese boy presented with a 2-year history of progressive blurring of vision in his right eye. There was no significant past ocular history. On examination, Snellen visual acuities were 6 ⁄60 in his left eye (OD) and 6 ⁄ 6 in his right eye (OS). Fundoscopy revealed extensive panretinal exudation with telangiectacic vessels (Fig. 1). Fluorescein angiography showed extensive areas of non-perfusion with characteristic light-bulb aneurysms (Fig. 2). A clinical diagnosis of Coats’ disease was made. The patient elected to proceed with intravitreal bevacizumab treatment after informed consent to the off-label use of this drug was gained from both the boy and his parents. Both the ocular (anterior-segment injury, cataract formation, retinal detachment, retinal pigment epithelial tear and acute vision loss) and systemic (cerebral infarction, hypertension and facial skin redness) risks of intravitreal bevacizumab were discussed (Shima et al. 2008). The patient received a single injection OD. Significant reduction in subretinal fluid and exudation was noted; therefore, focal argon laser photocoagulation to the telangiectactic vessels and areas of non-perfusion followed 2 weeks later. Further improvement in retinal exudation was noted and the patient remained stable at 1-year follow up, with visual acuities 6 ⁄ 45 OD and 6 ⁄ 6 OS (Fig. 3). Bevacizumab is a full-length humanized recombinant antibody against vascular endothelial growth factor (VEGF). Although it is approved for the treatment of colorectal, lung and breast cancer, there have been numerous reports of its safety and efficacy in the off-label treatment of choroidal neovascularisation (CNV) and other ischaemic-proliferative retinopathies such as diabetic retinal neovascularization (Avery et al. 2006; Kernt et al. 2007; Fang et al. 2008; Tonello et al. 2008). The intravitreal injection of pegaptanib sodium (another anti-VEGF molecule) has been shown to reduce VEGF levels in a patient with Coats’ disease (Sun et al. 2007). Only four other cases documenting the use of bevacizumab in the treatment of Coats’ disease have been described (Alvarez-Rivera et al. 2008; Cakir et al. 2008; Venkatesh et al. 2008). However, our case describes the benefits of using intravitreal antiVEGF in combination with subsequent laser photocoagulation. This strategy allows both the reduction of the subretinal fluid and exudation with the anti-VEGF prior to any subsequent laser, thereby potentially improving its efficacy. The optimal time period between intravitreal Fig. 1. Fundal photograph showing extensive subretinal fluid and exudation.

Haemorrhagic pigment epithelial detachment as a predictive feature of polypoidal choroidal vasculopathy in a Chinese population

PurposeTo determine the frequency of haemorrhagic pigment epithelial detachment (PED) among patients presenting with either polypoidal choroidal vasculopathy (PCV) or choroidal neovascularization (CNV) and calculate the degree to which the presence of a haemorrhagic PED can be used to predict the diagnosis of PCV.MethodsA retrospective review of 290 eyes of 253 patients presenting to the Singapore National Eye Centre with serosanguineous maculopathy. Patients underwent ophthalmologic examination including digital colour fundus photography and stereoscopic fluorescein angiography and indocyanine green angiography (ICGA). Classification into PCV or CNV was based on ICGA findings, and presence or absence of haemorrhagic PED was documented.ResultsIn total, 138 eyes of 123 patients were diagnosed with PCV and 152 eyes of 130 patients with CNV. A haemorrhagic PED was a significantly more common (P<0.001) presenting feature in PCV eyes (63, 45.7%) than CNV eyes (6, 3.9%) (odds ratio (OR) 20.4, 95% confidence interval (CI) 8.5–49.4). Age-related maculopathy was found significantly more frequently (P<0.001) in the unaffected fellow eye of CNV patients (57, 52.8%) than PCV patients (28, 22.8%) (OR 3.2, 95% CI 1.8–5.7).ConclusionsIn patients of Chinese ethnicity, a haemorrhagic PED is significantly more likely to be the presenting feature of PCV than CNV. Patients presenting with this clinical feature should make the clinician suspicious of an underlying diagnosis of PCV.

Toll-Like Receptor 3 Polymorphism rs3775291 Is Not Associated with Choroidal Neovascularization or Polypoidal Choroidal Vasculopathy in Chinese Subjects

Background/Aims: Age-related macular degeneration (AMD) is a leading cause of visual impairment. A single-nucleotide polymorphism (SNP; rs3775291) in the Toll-like receptor 3 (TLR3) gene has recently been implicated in the pathogenesis of AMD in Caucasian populations. The aim of this study was to examine this association in Chinese persons with choroidal neovascularization (CNV) secondary to AMD and polypoidal choroidal vasculopathy (PCV). Methods: This was an observational cross-sectional study in Singapore. Study subjects were of Chinese ethnicity and included patients with exudative maculopathy and normal control subjects. The diagnoses of CNV and PCV were made based on fundus examination, fluorescein angiography and indocyanine green angiography findings. Genomic DNA was extracted, and genotypes were determined by bidirectional DNA sequencing. We compared the allele and genotype frequencies between subjects with CNV and PCV with controls using the software PLINK. Results: A total of 246 subjects with exudative maculopathy (consisting of 126 with CNV and 120 with PCV) and 274 normal control subjects were recruited. The distribution of rs3775291 SNP genotypes for CNV and PCV was not significantly different from that for normal controls. Conclusion: This study indicates that the TLR3 rs3775291 gene polymorphism is not associated with CNV and PCV in Singaporean Chinese patients.

Transorbital brain injuries

A 20 year old man attended the accident and emergency department after an assault with a short bladed knife. He had sustained a stab wound to the right orbit. There was no other significant history. On examination he was alert and orientated with a Glasgow coma scale of 15. Snellen visual acuities were no perception of light right eye and 20/20 left eye. Inspection of the right orbit revealed a right upper lid laceration and an underlying penetrating eye injury. There was no other neurological deficit. Plain orbital radiographs were obtained but did not show any defects. However, in …