Advances of optical coherence tomography in myopia and pathologic myopia.

The natural course of high-axial myopia is variable and the development of pathologic myopia is not fully understood. Advancements in optical coherence tomography (OCT) technology have revealed peculiar intraocular structures in highly myopic eyes and unprecedented pathologies that cause visual impairment. New OCT findings include posterior precortical vitreous pocket and precursor stages of posterior vitreous detachment; peripapillary intrachoroidal cavitation; morphological patterns of scleral inner curvature and dome-shaped macula. Swept source OCT is capable of imaging deeper layers in the posterior pole for investigation of optic nerve pits, stretched and thinned lamina cribrosa, elongated dural attachment at posterior scleral canal, and enlargement of retrobulbar subarachnoid spaces. This has therefore enabled further evaluation of various visual field defects in high myopia and the pathogenesis of glaucomatous optic neuropathy. OCT has many potential clinical uses in managing visual impairing conditions in pathologic myopia. Understanding how retinal nerve fibers are redistributed in axial elongation will allow the development of auto-segmentation software for diagnosis and monitoring progression of glaucoma. OCT is indispensable in the diagnosis of various conditions associated with myopic traction maculopathy and monitoring of post-surgical outcomes. In addition, OCT is commonly used in the multimodal imaging assessment of myopic choroidal neovascularization. Biometry and topography of the retinal layers and choroid will soon be validated for the classification of myopic maculopathy for utilization in epidemiological studies as well as clinical trials.

Focal choroidal excavation in patients with central serous chorioretinopathy.

PURPOSE: To evaluate the prevalence and clinical features of focal choroidal excavation (FCE) in patients presenting with central serous chorioretinopathy (CSC). METHODS: This is a retrospective consecutive case series of consecutive patients with CSC who were referred for spectral domain optical coherence tomography (SD-OCT) between January 2010 and December 2011. Medical records were reviewed and clinical features including presence of FCE in SD-OCT, fluorescence angiography (FA), and indocyanine green angiography (ICGA) were studied. RESULTS: Among the 116 CSC patients assessed, FCE was found in 11 eyes of 7 (6.0%) patients. FCE was associated with subretinal fluid in six eyes of six patients and serous pigment epithelial detachment in three eyes of two patients. The mean central subfield retinal thickness of CSC eyes with FCE was 283.7 µm, compared with 377.5 µm for CSC eyes without FCE (Mann-Whitney U-test, P=0.020). Five FCE eyes of five patients had focal leakage on FA. Choroidal hyperpermeability on ICGA was found in seven CSC eyes with FCE, with four eyes showing hypofluorescent spot corresponding to the FCE. After a mean follow-up of 16 months, visual acuity of all 11 eyes with FCE remained stable or improved at the last follow-up. CONCLUSION: FCE is not an uncommon feature in patients with CSC and might be associated with choroidal hemodynamic disturbances.

FPR1 interacts with CFH, HTRA1 and smoking in exudative age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: To determine the genetic association of an inflammation-related gene, formyl peptide receptor 1 (FPR1), in exudative age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHODS: The coding region of FPR1 gene was sequenced in 554 unrelated Chinese individuals: 155 exudative AMD patients, 179 PCV patients, and 220 controls. Interactions and combined effects of FPR1 with complement factor H (CFH), high temperature requirement factor A1 (HTRA1), and smoking were also investigated. RESULTS: A total of 28 polymorphisms in FPR1 were identified. Single nucleotide polymorphisms (SNP) rs78488639 increased the risk to exudative AMD (P=0.043) and PCV (P=0.016), whereas SNP rs867229 decreased the risk to exudative AMD (P=0.0026), but not PCV. Homozygous G allele of rs1042229 was associated with exudative AMD (P=0.0394, odds ratio (OR)=2.27, 95% confident interval: 1.08-4.74), but not with PCV. Exudative AMD, but not PCV, was associated with the heterozygous genotypes of rs2070746 (P=0.019, OR=0.57) and rs867229 (P=0.0082, OR=0.54). Significantly, interactions were identified among FPR1 rs78488639, CFH rs800292, and HTRA1 rs11200638 in both exudative AMD and PCV. Combined heterozygous risk alleles of CFH rs800292 GA and FPR1 rs78488639 CA were posed to PCV (P=2.22 × 10(-4), OR=10.47), but not exudative AMD. Furthermore, FPR1 rs78488639 CA combining with HTRA1 rs11200638 and smoking was also predisposed risks to exudative AMD and PCV. CONCLUSION: FPR1 is associated with exudative AMD and PCV in a Hong Kong Chinese cohort. FPR1 rs78488639 interacted with CFH rs800292, HTRA1 rs11200638, and smoking, enhancing risk to exudative AMD and PCV.

Contribution of SNRNP200 sequence variations to retinitis pigmentosa.

PURPOSE: Mutations in the SNRNP200 gene have been reported to cause autosomal dominant retinitis pigmentosa (adRP). In this study, we evaluate the mutation profile of SNRNP200 in a cohort of southern Chinese RP patients. METHODS: Twenty adRP patients from 11 families and 165 index patients with non-syndromic RP with mixed inheritance patterns were screened for mutations in the mutation hotspots of SNRNP200. These included exons 12-16, 22-32, and 38-45, which covered the two helicase ATP-binding domains in DEAD-box and two sec-63 domains. The targeted regions were amplified by polymerase chain reaction and analyzed by direct DNA sequencing, followed by in silico analyses. RESULTS: Totally 26 variants were identified, 18 of which were novel. Three non-synonymous variants (p.C502R, p.R1779H and p.I698V) were found exclusively in patients. Two of them, p.C502R and p.R1779H, were each identified in one simplex RP patient, whereas p.I698V occurred in one patient with unknown inheritance pattern. All three residues are highly conserved in SNRNP200 orthologs. Nevertheless, only p.C502R and p.R1779H were predicted to affect protein function by in silico analyses, suggesting these two variants are likely to be disease-causing mutations. Notably, all mutations previously identified in other study populations were not detected in this study. CONCLUSIONS: Our results reveal a distinct mutation profile of the SNRNP200 gene in a southern Chinese cohort of RP patients. The identification of two novel candidate mutations in two respective patients affirmed that SNRNP200 contributes to a proportion of overall RP.

Long-term outcome of intravitreal anti-vascular endothelial growth factor therapy with bevacizumab or ranibizumab as primary treatment for subfoveal myopic choroidal neovascularization.

PURPOSE: To evaluate the long-term efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy as primary treatment for subfoveal myopic choroidal neovascularization (CNV). METHODS: In all, 37 treatment-naïve eyes of 37 patients with subfoveal myopic CNV who received intravitreal bevacizumab (n=22) or ranibizumab (n=15) injections with at least 2 years of follow-up were reviewed. All eyes received initial three loading doses of anti-VEGF at monthly intervals and retreatment was performed in persistent or recurrent CNV. Multivariate regression analyses were performed to determine the prognostic factors for visual outcome. RESULTS: The mean age was 57.3 years and the mean refractive error was -11.7 D. For all eyes, the mean logMAR best-corrected visual acuity improved from 0.86 (20/145) at baseline to 0.48 (20/60) at 2 years (P<0.001). The mean visual improvement for the bevacizumab and ranibizumab groups at 2 years was 2.8 and 5.1 lines, respectively (P=0.073). There was no significant difference in the proportion of eyes having visual gain of three or more lines or visual loss of three or more lines between the two groups. The mean number of injections was 3.8 for both bevacizumab and ranibizumab groups. Multivariate analyses showed that eyes with higher myopic refractive error were less likely to have visual gain after treatment (P=0.043), while size of CNV was negatively correlated with mean change in vision (P=0.046). CONCLUSIONS: Intravitreal anti-VEGF therapy resulted in long-term visual improvement in myopic CNV. The treatment efficacy in terms of visual gain and number of retreatment appeared to be similar between bevacizumab and ranibizumab.

Application of multifocal visual evoked potentials in the assessment of visual dysfunction in macular diseases.

PURPOSE: To evaluate the use of AccuMap multifocal visual evoked potentials (mfVEP) in visual dysfunction caused by macular diseases. METHODS: Forty-eight eyes with known macular diseases underwent AccuMap mfVEP and microperimetry 1 (MP1) assessments. Evaluation of mfVEP abnormality was based on an amplitude deviation probability plot and the AccuMap Severity Index (ASI). Correlation analyses of the mean mfVEP amplitude corresponding to a radius of 2°, 5°, and 10° of the central visual field, minimum angle of resolution best-corrected visual acuity (BCVA), and MP1 mean sensitivity of the corresponding areas were performed. RESULTS: Among the 48 affected eyes, AccuMap mfVEP detected an abnormality of the central visual field in 45 eyes, with a sensitivity of 93.8%. The mean mfVEP amplitudes within a radius of 2°, 5°, and 10° of the central visual field were found to be positively correlated with BCVA (P<0.01 for all groups). The mean amplitudes also positively correlated with the MP1 mean sensitivity value of the corresponding visual field (P<0.01 for all groups). In the group with stable fixation or predominantly central fixation, the mean mfVEP amplitudes did not correlate with the BCVA or the MP1 mean sensitivity value. Regardless of the fixation status, the ASI was found to correlate with both the BCVA and the total MP1 mean defect value. CONCLUSION: Objective perimetry using AccuMap mfVEP might be applied in the assessment of macular function, with the ASI offering a potentially useful indicator for evaluating macular dysfunction.

Multifocal electroretinography changes in patients on ethambutol therapy.

PURPOSE: To evaluate the multifocal electroretinography (mfERG) changes in patients on ethambutol therapy. METHODS: A cross-sectional observational study of 17 visually asymptomatic patients receiving antituberculosis therapy with ethambutol. Patients underwent complete ophthalmic examination and mfERG recordings. The first-order mfERG N1 and P1 response amplitudes and implicit times of six concentric rings were analysed and compared with 17 normal age-similar controls. Correlation analyses were performed between the patients' mfERG parameters with parameters of ethambutol usage (daily dose of ethambutol per body weight, duration of ethambutol therapy, cumulative dose of ethambutol, and cumulative dose of ethambutol per body weight). RESULTS: The mean duration of ethambutol therapy was 3.6 months (range: 2-9 months) and the mean daily dose per body weight was 13.2 mg/kg/day. Analysis of response amplitude measures showed no significant difference in the mfERG N1 and P1 response amplitudes between the ethambutol and control groups at all ring eccentricities (P>0.05). For implicit times, there were significant delays in the mfERG P1 implicit times of rings 4-6 in the ethambutol group compared with controls (P=0.012 to P=0.041). Correlation analyses showed no significant correlation between the mfERG and ethambutol parameters (P>0.05). CONCLUSIONS: The mfERG findings suggested that visually asymptomatic patients receiving ethambutol therapy might have localized mild electrophysiological changes involving the peripheral macula. These changes might be related to localized alteration of metabolism or physiological changes associated with ethambutol therapy.

Effects of the duration of initial oral corticosteroid treatment on the recurrence of inflammation in Vogt-Koyanagi-Harada disease.

PURPOSE: To evaluate the effects of the duration of oral corticosteroid treatment on the recurrence of inflammation in Vogt-Koyanagi-Harada (VKH) disease. METHODS: Retrospective analysis of 35 VKH patients who received oral corticosteroid during the first attack of VKH with a minimum follow-up of 6 months. Patients were divided into two groups on the basis of the oral corticosteroid treatment duration of less than 6 months or 6 months or more. Kaplan-Meier survival and Cox-regression analyses were carried out to compare the recurrence rates of inflammation in the two groups. RESULTS: The mean age of onset was 42.5 years and the mean follow-up duration was 3.6 years. During the follow-up period, 10 (58.8%) of the 17 patients who received oral corticosteroid for less than 6 months compared with 2 (11.1%) of the 18 patients who had treatment for 6 months or more developed recurrence of inflammation (P=0.003). Cox-regression analysis showed that the duration of oral corticosteroid treatment for less than 6 months was the only significant risk factor for recurrence of VKH after adjustment for age, gender, and the initial dosage of oral corticosteroid treatment (adjusted odds ratio=8.8, P=0.008). Patients who received oral corticosteroid treatment for less than 6 months were also more likely to have one eye with visual acuity of 20/200 or worse (P=0.016). CONCLUSIONS: Early withdrawal of oral corticosteroid is associated with increased risk of recurrence of VKH and worse visual prognosis. Oral corticosteroid should be tapered off slowly and maintained for at least 6 months for the treatment of acute VKH.

Intravitreal bevacizumab (Avastin) for myopic choroidal neovascularisation: 1-year results of a prospective pilot study.

AIM: The aim of the study was to examine the 1-year results of intravitreal bevacizumab for myopic choroidal neovascularisation (CNV). METHODS: Twenty-nine eyes of 29 patients with myopic CNV were prospectively recruited to receive three initial monthly intravitreal bevacizumab injections. Three additional monthly injections were performed in eyes with persistent or recurrent CNV after 3 months. RESULTS: The mean spherical equivalent refractive error was -10.0 D. Sixteen eyes had previous photodynamic therapy (PDT) and 13 eyes had no prior PDT. All patients completed follow-up at 1 year. Following the initial three bevacizumab injections, 27 (93.1%) eyes had angiographic closure and two (6.9%) required further treatment. Two additional patients required re-treatment for CNV recurrence between 6 and 9 months. The mean baseline logarithm of the minimum angle of resolution (logMAR best-corrected visual acuity) was 0.62 (20/83), which improved to 0.38 (20/48) at 12 months (p<0.001). The mean visual improvement was 2.4 lines and 21 (72.4%) eyes had improvement of > or =2 lines. Optical coherence tomography showed significant reduction in central foveal thickness following treatment. Eyes without previous PDT were more likely to gain > or =2 lines after treatment than eyes that had previous PDT (p = 0.010). CONCLUSIONS: The 1-year outcomes confirmed the results of previous short-term studies that intravitreal bevacizumab is effective for myopic CNV, with a high proportion of patients sustaining visual gain after treatment.

Intravitreal bevacizumab (Avastin) with or without photodynamic therapy for the treatment of polypoidal choroidal vasculopathy.

AIM: To evaluate the efficacy of intravitreal bevacizumab (Avastin) with or without verteporfin photodynamic therapy (PDT) in the treatment of polypoidal choroidal vasculopathy (PCV). METHODS: Fifteen eyes of 15 patients with symptomatic PCV who received three monthly intravitreal bevacizumab were retrospectively reviewed. Subsequent retreatments with intravitreal bevacizumab and/or PDT were performed in patients with recurrent or persistent polypoidal lesions on indocyanine green angiography (ICGA), and persistent or recurrent subretinal fluid. RESULTS: The mean follow-up duration was 12.8 months. At 3 months, the mean logMAR BCVA improved from 0.61 to 0.51 (p = 0.014), and the mean CFT reduced from 347 microm to 247 microm (p = 0.015). Despite the visual and anatomical improvements, persistent polyps were present in ICGA of all eyes at 3 months. At the last follow-up, mean BCVA remained at 0.51 after additional treatment with intravitreal bevacizumab and/or PDT (p = 0.022). Patients who had subsequent PDT were less likely to have persistent polypoidal lesions on ICGA at the last visit (p = 0.041). CONCLUSIONS: Intravitreal bevacizumab appeared to result in stabilisation of vision and reduction of exudative retinal detachment in PCV patients. However, intravitreal bevacizumab monotherapy had limited effectiveness in causing regression of the polypoidal lesions in ICGA, and additional PDT appeared to be useful for treating these lesions.

Peripheral and posterior pole retinal lesions in association with high myopia: a cross-sectional community-based study in Hong Kong.

PURPOSE: To evaluate the prevalence and factors associated with posterior pole and peripheral retinal lesions in Chinese subjects with high myopia. METHODS: Three hundred and thirty-seven asymptomatic adults with high myopia of refractive error

Decreasing efficacy of repeated intravitreal triamcinolone injections in diabetic macular oedema.

BACKGROUND/AIM: Intravitreal triamcinolone (IVTA) results in transient improvements in diabetic macular oedema (DMO), necessitating repeated injections. The authors report a case series of 10 eyes of 10 patients with DMO, who received a repeat injection of 4 mg IVTA, at least 26 weeks after the first injection of the same dose. METHOD: Pre-injection and at 2, 4, 9, and 17 weeks post-injection, best corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography, after the first and repeat injections, were compared using paired t test. Side effects were monitored. RESULTS: BCVA, CFT, intraocular pressure (IOP), and cataract scores were not significantly different before initial and repeat injections (given at 32.5 (SD 3.5) weeks after the first injection). Transient improvements of BCVA and CFT were achieved after both injections. However, after the repeat injection, the BCVA was significantly worse at all time points (p<0.05) and so were the best achieved CFT and the CFT at 4 weeks post-injection (p = 0.034 and 0.011 respectively), compared with the initial injection. Post-injection maximum IOPs and increase in cataract scores were not significantly different between the two injections. CONCLUSION: A repeat injection of 4 mg of IVTA may not be as effective as an initial injection for the treatment of DMO.

Safety enhanced photodynamic therapy with half dose verteporfin for chronic central serous chorioretinopathy: a short term pilot study.

AIM: To evaluate short term safety of an enhanced photodynamic therapy (PDT) protocol with half dose verteporfin for treating chronic central serous chorioretinopathy (CSC). METHODS: 20 eyes of 18 patients with symptomatic chronic CSC underwent PDT using 3 mg/m2 verteporfin. Verteporfin was infused over 8 minutes followed by indocyanine green angiography guided laser application 2 minutes later. Serial optical coherence tomography (OCT) and multifocal electroretinography (mfERG) recordings were performed before PDT, at 4 days, 2 weeks, and 1 month after PDT. The best corrected visual acuity (BCVA), OCT central retinal thickness, and mean mfERG response amplitudes and peak latencies were compared longitudinally. Subgroup analysis was further performed for eyes with or without pigment epithelial detachment (PED). RESULTS: At 1 month after PDT, the median BCVA improved from 20/40 to 20/30 (p = 0.001). The mean central retinal thickness also reduced from 276 microm to 158 microm (p < 0.001) and 17 (85%) eyes had complete resolution of serous retinal detachment and/or PED. MfERG showed no significant changes in the mean N1 and P1 response amplitude and latency for all eyes. Subgroup analysis demonstrated that eyes without PED had a significant increase in the mean central mfERG P1 response amplitude with reduction in P1 peak latency at 1 month post-PDT. For eyes with PED, transient reduction in the mean central P1 response amplitude was observed at 4 days post-PDT. CONCLUSIONS: The modified safety enhanced PDT protocol with half dose verteporfin appeared to be a beneficial treatment option for patients with chronic CSC, especially in eyes without serous PED. Further controlled study is warranted to demonstrate the long term safety and efficacy of this treatment option.

Combined photodynamic therapy and intravitreal triamcinolone injection for the treatment of subfoveal choroidal neovascularisation in age related macular degeneration: a comparative study.

AIM: To evaluate the outcomes of combined intravitreal triamcinolone (IVTA) and photodynamic therapy (PDT) with verteporfin in the treatment of subfoveal choroidal neovascularisation (CNV) caused by age related macular degeneration (AMD). METHODS: 48 eyes from 48 patients with subfoveal CNV caused by AMD were prospective recruited, with 24 eyes treated with combined PDT with IVTA and compared with a control group of 24 eyes which received PDT monotherapy. In the combined treatment group, IVTA was performed immediately after PDT as an outpatient procedure. The mean number of treatments, mean logMAR best corrected visual acuity (BCVA), mean line of visual acuity changes, and proportion of patients without moderate visual loss at 1 year were compared between the combined and monotherapy groups. RESULTS: At 1 year the logMAR BCVA for the PDT with IVTA group changed from 0.88 to 0.95 (p = 0.32 compared with baseline), whereas the logMAR BCVA for the monotherapy group reduced from 0.74 to 1.09 (p<0.001 compared with baseline). A significantly higher proportion of patients who had PDT with IVTA did not develop moderate visual loss at 1 year compared with the monotherapy group (70.8% and 33.3% respectively, p = 0.009). Eyes which had combined treatment had significantly fewer lines lost compared with monotherapy alone (0.7 and 3.5 lines respectively, p = 0.015). Subgroup analysis showed that PDT with IVTA is effective in preventing visual loss in both predominately classic and occult CNV groups. The mean number of treatments for the combined and monotherapy groups was 1.5 and 1.96 respectively (p = 0.076). CONCLUSIONS: Combined PDT with IVTA appeared more effective statistically at 12 months for stabilisation of vision (<3 logMAR lines change) compared with PDT monotherapy. Further randomised control trials might be justified to conclude the efficacy of PDT with IVTA.

A prospective study on trypan blue capsule staining under air vs under viscoelastic.

AIM: To compare the safety and effectiveness of trypan blue capsule staining under air vs under viscoelastic. METHODS: A total of 52 consecutive patients planned for phacoemulsification of white mature cataract were randomly assigned to trypan blue staining under air or under viscoelastic. Perioperative changes in best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell density (ECD) were compared between the two groups. The differences in operating and phacoemulsification times, staining pattern, and complications between the two groups were also recorded. RESULTS: Phacoemulsification of white mature cataract was performed in 50 (96%) eyes. The median preoperative BCVA was hand movement. No significant differences in the baseline characteristics were found between the two groups. At 3 months after phacoemulsification, the median BCVA improved to 0.8. The mean CCT returned to preoperative level by 1 month postoperatively and the mean ECD loss was 11.9% 3 months postoperatively. No significant differences in median BCVA, mean phacoemulsification and operation times, mean CCT, and mean ECD were found between the two groups. CONCLUSIONS: Trypan blue staining of the anterior lens capsule under air or under viscoelastic were similarly effective and safe methods for the phacoemulsification of white mature cataract.

Retinal ganglion cells toxicity caused by photosensitising effects of intravitreal indocyanine green with illumination in rat eyes.

AIM: To investigate the effects of indocyanine green (ICG) with or without illumination on rat retinal ganglion cells (RGC) and retinal morphology. METHODS: Intravitreal injections of 1.0 mg/ml ICG solution were performed in rat eyes with or without subsequent illumination for 5 minutes. Eyes in the control group had intravitreal injections of balanced salt solution with illumination. Retrograde labelling of RGC with 6% Fluoro-Gold was performed 1 month later and RGC densities were compared between the three groups. Light microscopy with measurements of outer nuclear layer (ONL) and inner nuclear layer (INL) thicknesses were also performed and compared. RESULTS: Eyes with ICG without illumination showed insignificant reduction in RGC density compared with the control group (p = 0.28), whereas a significant decrease in RGC density was found in eyes that had ICG injection with illumination (p = 0.036). A significant increase in ONL thickness was also observed in the ICG with illumination treated eyes compared with the ICG without illumination and the control groups (p<0.001). No significant difference in INL thickness was observed between the three groups. CONCLUSIONS: Intravitreal injection of 0.1 mg/ml ICG in rat eyes followed by illumination resulted in photosensitising toxicity to RGC. Lower ICG concentration or illumination level should be considered when performing ICG assisted macular surgery.

Choroidal neovascularisation in pathological myopia: an update in management.

Choroidal neovascularisation (CNV) secondary to pathological myopia is an important cause of significant visual impairment in young and middle aged adults globally and is particularly prevalent in Asian populations. In the past few years, there have been rapid advancements in the different treatments for myopic CNV. The purpose of this perspective is to give an overview of the natural history of myopic CNV and the various treatment options including laser photocoagulation, photodynamic therapy, sub-macular surgery, and macular translocation surgery. Future directions in the management of myopic CNV are also discussed.