C-reactive protein and complement factor H polymorphism interaction in advanced exudative age-related macular degeneration

Purpose

To determine the association of C-reactive protein (CRP) and complement factor H (CFH) gene with exudative age-related macular degeneration (AMD) and any possible interaction among these factors.

Methods

In this case–control study, 139 unrelated patients with exudative AMD and 123 non-AMD controls were recruited. Blood sample was taken for analysis of the CRP levels and DNA testing. DNA fragments of CFH gene variants containing 4 single nucleotide polymorphisms including rs800292, rs1061170, rs2274700, and rs3753395 were assessed. A CRP level of ≥3 mg/L was considered as elevated. The association of elevated CRP and CFH gene variants polymorphism with exudative AMD was compared between the groups.

Results

Mean age was 72.6 ± 6.4 for controls and 74.9 ± 7.4 for case group (P = 0.006). The difference between CRP levels in cases and controls was not statistically significant (P = 0.055). However, Y402H variant of CFH in both homozygous and heterozygous carriers C allele was significantly more frequent among exudative AMD patients than controls, 32.1 versus 6.5 % (P < 0.001). Evaluating various CRP levels in patients with CC and non-CC genotypes disclosed that in CC genotype group, higher CRP level (>3 mg/L) was associated with higher risk of developing exudative AMD (OR = 12.0, CI: 1.5–98.8) compared with the control group.

Conclusion

This study disclosed no difference in CRP levels per se between exudative AMD patients with control group. However, higher levels of CRP in the presence of C allele of Y402H might confer more risk for the development of exudative AMD.

     

Effects of vitreomacular adhesion on ranibizumab treatment in Japanese patients with age-related macular degeneration

Purpose

To investigate the effects of vitreomacular adhesion (VMA) on intravitreal ranibizumab treatment in Japanese patients with exudative age-related macular degeneration (AMD).

Methods

This was a retrospective comparative study that included 123 eyes from 123 patients with exudative AMD. The presence or absence of VMA was examined by spectral domain optical coherence tomography. The association of VMA with best-corrected visual acuity (BCVA) and central retinal thickness (CRT) at 3, 6, and 12 months after ranibizumab treatment was evaluated.

Results

In the group of eyes without VMA [VMA(?)], the mean BCVA was 0.41 logMAR at baseline and significantly improved to 0.28, 0.30, and 0.29 logMAR at 3, 6, and 12 months following the initiation of treatment (P < 0.0001, <0.0001, <0.0001), respectively. In the group of eyes with VMA [VMA(+)], the mean BCVA was 0.42 logMAR at baseline, and there was no improvement at any of the measurement time-points during the follow-up period [0.39, 0.40, and 0.39 logMAR at 3, 6, and 12 months (P = 0.53, 0.75, 0.67), respectively]. The mean baseline CRT in the VMA(?) and VMA(+) groups was 326 and 370 µm, respectively, decreasing to 195 and 293 µm (P < 0.0001 and P = 0.0070), respectively, at 12 months. A better baseline BCVA was associated with poor visual response to intravitreal ranibizumab.

Conclusions

Our study of Japanese patients with AMD managed in real-world clinical practice revealed that both VMA and BCVA at baseline were associated with a poor visual response to intravitreal ranibizumab. These results are in agreement with previously reported findings for other ethnic groups.     

Factors influencing the exudation recurrence after cataract surgery in patients previously treated with anti-vascular endothelial growth factor for exudative age-related macular degeneration

Purpose

To investigate factors influencing exudation recurrence following cataract surgery in patients already treated with anti-vascular endothelial growth factor (VEGF) agents for exudative age-related macular degeneration (AMD).

Methods

A retrospective review of medical records was performed for patients who underwent cataract surgery and had been previously treated with anti-VEGF for exudative AMD. Visual acuity was examined before surgery and 1 and 6 months after surgery. The time between diagnosis and surgery, and the exudation-free period before surgery were examined and compared between patients who had exudation recurrence and those that did not.

Results

Thirty-nine eyes of 39 patients were included in analyses. The logarithm of the minimum angle of resolution visual acuity was 1.02?±?0.58 and had significantly improved 1 month (0.81?±?0.62, P?P?=?0.001) following surgery. Both the diagnosis-to-surgery period (P?=?0.001) and the preoperative exudation-free period (P?Conclusions Cataract surgery was beneficial in patients previously treated with anti-VEGF for exudative AMD. Our data suggests that cataract surgery should be performed after a sufficiently long exudation-free period to minimize exudation recurrence. But larger prospective studies are required to draw definitive clinical guidelines.     

Multimodal evaluation of macular function in age-related macular degeneration

Objective

To evaluate macular function using multimodality in eyes with age-related macular degeneration (AMD) at various stages.

Methods

Macular function in 20 control eyes (20 subjects), 17 eyes (17 patients) with large drusen, 18 eyes (18 patients) with drusenoid pigment epithelial detachment (PED), and 19 eyes (19 patients) with neovascular AMD was examined using a Landolt chart for visual acuity; retinal sensitivity was measured by microperimetry; and focal macular electroretinography (fmERG) was performed. In all of these eyes, retinal morphology was examined using optical coherence tomography.

Results

Eyes with neovascular AMD showed morphologic changes in the neurosensory retina as well as marked deterioration of macular function in all parameters measured with a Landolt chart, fmERG, and microperimetry. Eyes with large drusen showed only minimal morphologic changes in the neurosensory retina. In this large drusen group, although retinal sensitivity at the central point was significantly decreased (P = 0.0063), the other parameters of macular function were well preserved. In eyes with drusenoid PED, the structure of the neurosensory retina was well preserved, while the foveal thickness was significantly increased (P = 0.013). The macular function of these eyes was significantly deteriorated, with the VA, amplitude of the a-wave and b-wave, and retinal sensitivity being markedly decreased. In addition, the area of PED correlated with the latency of the a-wave and b-wave and with the retinal sensitivity within the central 4° or 8° region.

Conclusion

Multimodal evaluation demonstrated a significant decrease in macular function in drusenoid PED and in neovascular AMD.     

Impact of injection techniques on intraocular pressure (IOP) increase after intravitreal ranibizumab application

Purpose

To examine the influence of different intravitreous injection techniques on the short-term intraocular pressure (IOP) in patients with exudative age-related macular degeneration (AMD) receiving 0.05 ml ranibizumab (Lucentis®) in the supine position.

Methods

Forty-five eyes (45 patients, 16 male, 29 female, mean age: 78 years) received intravitreal ranibizumab injections for treatment of exudative AMD (0.05 ml?=?0.5 mg). A total of 31 patients received a standard straight scleral incision, and 14 were injected using the tunneled sclera technique. IOP was measured by Schiøtz tonometry immediately pre-and postoperatively, and the amount of subconjunctival reflux was documented using a semi-quantitative scale. Twenty-three eyes were phakic, and the remaining 22 were pseudophakic. No history of glaucoma was present. The Wilcoxon matched-pairs test was used for comparisons.

Results

The mean preoperative IOP was 22.4?±?5.5 mmHg in the supine position. Immediately after the injection, the IOP increased to 47.9?±?15.1 (range 23–82). The mean difference between preoperative IOP and immediately after the injection was 25.5?±?13.6 mmHg. The mean IOP increase in eyes receiving a standard straight scleral incision was 21.9?±?14.2 mmHg (median 22.3) versus 33.5?±?7.2 mmHg (median 34.7) in the tunneled scleral incision group (p?=?0.001).

Conclusions

IOP increased significantly in a considerable number of patients after receiving 0.05-ml intravitreal ranibizumab injections. This increase was dependent on the intravitreal injection technique and was significantly higher if a tunneled scleral injection was performed.     

Genetic and clinical factors associated with reticular pseudodrusen in exudative age-related macular degeneration

Backgrounds

Reticular pseudodrusen (RPD) is considered to be a distinct entity from soft drusen and a risk factor for age-related macular degeneration (AMD). In the present study, we investigate the genetic and clinical factors associated with reticular pseudodrusen (RPD) in patients with exudative AMD, including polypoidal choroidal vasculopathy (PCV), typical neovascular AMD, and retinal angiomatous proliferation (RAP).

Methods

The presence or absence of RPD was studied among 408 patients with exudative AMD in at least one eye, and the clinical characteristics of those with RPD were investigated as well as genetic polymorphisms of ARMS2 A69S (rs10490924) and CFH I62V (rs800292). Subfoveal choroidal thickness was also evaluated in a limited number of subjects using the EDI mode of spectral-domain optical coherence tomography.

Results

The prevalence of RPD was significantly higher in RAP eyes than in typical neovascular AMD or in PCV eyes (38.2 % of 26 eyes, 13.6 % of 132 eyes and 0 % of 250 eyes respectively, P?P?P?P?ARMS2 A69S was significantly higher in eyes with RPD than in those without RPD (85.7 % vs 63.8 %, P?=?0.0009), although the frequency of CFH I62V was not significantly different between those with and without RPD. Logistic regression analysis revealed that age (odds ratio [OR]:1.10; 95 % confidence interval [CI]: 1.04–1.18; p?=?0.002), female gender (OR:4.26; 95%CI: 1.72–10.4; p?=?0.002), T-allele at ARMS2 A69S (OR: 3.23; 95%CI: 1.36–7.68; p?=?0.008) and RAP (OR: 4.25; 95%CI:1.49–12.1; p?=?0.007) were risk factors for RPD.

Conclusions

Among eyes with exudative AMD, RPD is more common in eyes with RAP having a thin choroid at the fovea, especially in old, female patients with the risk variant of ARMS2 A69S.     

Efficacy of intravitreal aflibercept in Japanese patients with exudative age-related macular degeneration

Purpose

To clarify the efficacy of aflibercept for treating exudative age-related macular degeneration (AMD).

Methods

We prospectively studied 47 eyes with AMD. Forty-seven patients (mean age 72.2 years) received three consecutive monthly intravitreal aflibercept injections followed by an injection every 2 months until 12 months. The primary outcome was the 12-month visual results compared with baseline; the secondary outcomes were the prevalence of geography atrophy (GA), a dry macula at month 12, and anatomic changes on optical coherence tomography.

Results

The mean logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA) in 27 eyes with typical AMD and 20 eyes with polypoidal choroidal vasculopathy (PCV) significantly (p < 0.0001, p < 0.05, respectively) improved from 0.60 to 0.32 at baseline to 0.29 and 0.21 at month 12. At month 12, 22 (81.5 %) eyes with typical AMD and 17 (85 %) eyes with PCV had dry macula. The subfoveal choroidal thicknesses in typical AMD and PCV decreased significantly (p < 0.0001 for both comparisons) from 241 ± 118 and 294 ± 76 μ at baseline to 198 ± 104 and 244 ± 84 μ at month 12. Progressing or new GA was seen in three eyes with typical AMD and one eye with PCV; the mean change in the BCVA was significantly (p = 0.0026) worse at month 12. No other complications developed.

Conclusion

Intravitreal aflibercept significantly improved VA and anatomic changes in typical AMD and PCV over 12 months. Development of GA might be a risk for declining VA.

     

Long-term intraocular pressure changes after vitrectomy for epiretinal membrane and macular hole

Background

To investigate long-term intraocular pressure (IOP) changes after vitrectomy for epiretinal membrane (ERM) or macular hole (MH).

Methods

We retrospectively reviewed the medical records of 57 eyes with ERM and 61 eyes with MH that underwent vitrectomy. IOP levels and changes at 1, 3, 6, 12 months, and the final visit from baseline were evaluated in vitrectomized eyes and non-vitrectomized fellow eyes.

Results

In the ERM group, the mean follow-up period was 29.3 months; the mean preoperative IOP in the operated eyes was 12.9?±?2.5 mmHg and the final IOP was 13.2?±?2.9 mmHg. In the MH group, the mean follow-up period was 25.6 months; the mean preoperative IOP in the operated eyes was 13.3?±?2.5 mmHg and the final IOP was 14.0?±?3.2 mmHg. The mean final IOP of the fellow unoperated eyes was 13.0?±?2.5 mmHg in the ERM group and it was 12.9?±?3.2 mmHg in the MH group. A significant difference was found between the operated eyes and fellow eyes at the final visit in the MH group (P?<?0.01) but not in the ERM group (P?=?0.40). MH group was significantly at high risk of IOP increase after vitrectomy (P?<?0.01).

Conclusions

IOP increase after vitrectomy was found in some eyes with MH during long-term follow-up but it was unlikely in eyes with ERM.     

Effect of aflibercept in patients with age-related macular degeneration

The purpose of this study was to evaluate the efficacy of standard induction therapy with intravitreal aflibercept (IVA) in patients with exudative age-related macular degeneration (AMD) at 6 months after completion of induction therapy. Eleven eyes with typical AMD (tAMD) and 13 eyes with polypoidal choroidal vasculopathy (PCV) received three monthly doses of IVA (2 mg/0.05 ml in weeks 0, 4, and 8) for treatment of exudative AMD. Best-corrected visual acuity (BCVA) was measured, and optical coherence tomography was performed at baseline and at each monthly visit until 6 months after IVA. Treatment failure was defined as persistent or recurrent AMD that presented with cystoid macular edema, serous retinal detachment, and pigment epithelium detachment. Mean logMAR BCVA was improved from 0.62 ± 0.46 at baseline to 0.54 ± 0.43 at 6 months after IVA (p < 0.05). The success rate was 95.8 % at 3 months and 75.0 % at 6 months after IVA. Failure of IVA was positively associated with the absence of PVD before treatment (r = 0.35) and with the AMD type (tAMD, r = 0.43) by univariate analysis. Cox proportional hazards analysis demonstrated that the absence of PVD before treatment was associated with an increased risk of failure of IVA (OR = 33.17, p = 0.0219). Three months of induction IVA achieved a high success rate in patients with AMD monitored for up to 6 months. Factors associated with failure of IVA were the absence of PVD and the presence of tAMD. Accordingly, continuation of IVA following induction therapy may be beneficial to manage AMD in patients with tAMD or those without PVD.     

Effect of cataract surgery in patients with neovascular age-related macular degeneration: further evidence from disciform scars

Purpose

To evaluate the effect of cataract surgery on disease activation and visual outcomes in neovascular age-related macular degeneration (AMD).

Methods

In this retrospective case–control study, study arm consisted of neovascular AMD patients, who underwent phacoemulsification surgery. Patients did not have any disease activation at least 6 months before the inclusion, and all had at least 12-month follow-up thereafter. Control group consisted of phakic patients, who did not undergo eye surgery during the study period. Primary outcomes were the presence of the disease activation and the change in best-corrected visual acuity (BCVA).

Results

A total of 114 neovascular AMD patients [55 (48%) in exudative group and 59 (52%) in disciform group] were included. Preoperative logMAR BCVA was significantly improved after cataract surgery [0.8 (0.6–1.0) vs. 0.4 (0.4–0.7), P < 0.001 in exudative AMD; 1.85 (1.1–1.9) vs. 1.09 (0.8–1.9), P = 0.001 in disciform scar], but this improvement was not maintained during the study period in patients with both exudative AMD and disciform scar [0.6 (0.3–1.1), P = 0.313 in exudative AMD; 1.30 (1–1.9), P = 0.03 in disciform scar]. The incidence of disease activation was not statistically significant between surgery and control groups in patients with exudative AMD [5 (25%) patients in surgery group and 8 (22%) patients in the control group, P = 0.886, Cox proportional hazards regression analysis]. In disciform scar, disease activation was observed in 4 (17%) patients in the surgery group; however, no patient in the control group had disease activation (P = 0.009, HRs could not be estimated, 95% CI 0.001–43.49, Cox proportional hazards regression analysis).

Conclusion

Cataract surgery has benefit on early postoperative visual improvement in patients with neovascular AMD. The incidence of disease activation was not affected after surgery in exudative AMD.

     

Photoreceptor inner and outer segment layer thickness in multiple evanescent white dot syndrome

Purpose

To evaluate the photoreceptor inner and outer segment layer thickness in eyes with MEWDS.

Design

Prospective, non-comparative, observational case series. The follow-up duration was 4 months.

Methods

Four women were diagnosed with unilateral MEWDS. The ages of the patients were 25, 24, 35, and 40 years. The retinal microstructure was assessed by spectral-domain optical coherence tomography (SD-OCT). The thickness of the photoreceptor inner (IS) and outer (OS) segments and sum of them (IS + OS) at the fovea were analyzed.

Results

The visual acuity was reduced in three of four eyes at the acute phase. SD-OCT showed that the border of IS and OS (IS/OS) line and the cone outer segment tips (COST) line in the macula area were not detected in all four eyes. The IS + OS thickness was 50.3?±?5.6 μm and that of the healthy fellow eyes was 73.5?±?7.0 μm (n?=?4 eyes). The thickness of the IS was 27.8?±?2.6 μm and that of the OS was 45.8?±?7.3 μm. In all eyes, there was a spontaneous improvement of the visual acuity. SD-OCT showed a recovery of only the IS/OS line in the macular area, but the COST line was not visible in three cases. The mean IS + OS thickness increased to 56.0?±?7.9 μm (n?=?4), IS?=?26.0?±?2.0 μm (n?=?3), and OS?=?30.1?±?8.7 μm (n?=?3) in the early recovery phase, and to 64.8?±?9.3 μm (n?=?4), IS?=?28.5?±?1.7 μm (n?=?4), and OS?=?36.3?±?7.9 μm (n?=?4) in the late recovery phase. The mean inner and outer segment thickness remained unchanged in the fellow eyes.

Conclusion

Eyes with MEWDS have changes in the photoreceptor microstructures. The change in the IS + OS thickness during the natural recovery course might be due to an increase in the OS length.     

Enhanced depth imaging of the choroid in patients with neovascular age-related macular degeneration treated with anti-VEGF therapy versus untreated patients

Purpose

To compare the subfoveal choroidal thickness (SFCT) between patients with neovascular age-related macular degeneration (nAMD) who had multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents and those with treatment-naïve nAMD.

Methods

This retrospective case–control study included 15 patients in group 1 (nAMD in one eye which had received at least three anti-VEGF injections and early AMD in the fellow eye) and 15 patients in group 2 (newly diagnosed nAMD in one eye which had not received any treatment and early AMD in the fellow eye). They underwent enhanced depth imaging optical coherence tomography (OCT), and two OCT readers manually measured the SFCT. Inter-ocular difference in SFCT (nAMD eye minus fellow eye) was calculated for each patient.

Results

The nAMD eyes in group 1 had received a median (range) of four (3–8) intravitreal injections of anti-VEGF agents, and the OCT scans were performed at a median (range) of 9 (4–17) months after the first injection. The median inter-ocular difference in SFCT in groups 1 and 2 were not significantly different (13.5 and 3.0 μm in groups 1 and 2 respectively, p?=?0.60). There was also no statistically significant difference in SFCT between nAMD and fellow eyes (p?=?0.16), although there was a trend for greater median SFCT in the nAMD eyes.

Conclusion

The data from this small cohort suggests that no gross reduction in SFCT appears in nAMD patients after a time interval of at least 4 months between initiating repeated treatment with anti-VEGF therapy and OCT imaging. However, a study with a much larger sample size or longitudinal design is required to detect possible small fluctuations in SFCT in nAMD eyes receiving anti-VEGF therapy.     

Changes in reticular pseudodrusen area in eyes that progressed from early to late age-related macular degeneration

Objective

This retrospective cohort study utilized 3 imaging modalities to analyze quantitatively reticular pseudodrusen (RPD) area changes in eyes that progressed from early to late age-related macular degeneration (AMD).

Methods

Subjects with AMD, unilateral choroidal neovascularization (CNV), and early AMD with RPD in the fellow eye (the study eye) were included. The study eyes underwent indocyanine green angiography (ICGA), near-infrared reflectance (NIR-R), and short-wavelength autofluorescence (AF) imaging of the macula at baseline and at follow-up. Study eyes were analyzed for RPD and for the development of late AMD–CNV and/or geographic atrophy (GA). RPD area was measured at baseline and at follow-up as a percentage of the 30-degree field.

Results

During the study period (mean follow-up time 23.5 ± 5.0 months), 12/31 study eyes developed CNV and 4/31 developed GA. In the eyes that developed CNV, there was a statistically significant decrease in mean RPD area over the follow-up period as seen on AF (P < 0.01) and NIR-R (P = 0.01), and the decrease in mean RPD area approached statistical significance on ICGA (P = 0.08).

Conclusion

Using 3 en face imaging techniques, we demonstrate that RPD undergo dynamic spatiotemporal changes in eyes that progress from early AMD to CNV, namely a decrease in the area of lesions detected.

     

Risk factors for exudative age-related macular degeneration in a large French case–control study

Purpose

The purpose of the CAP (Creteil AMD PHRC-funded) Study was to analyze risk factors of exudative age-related macular degeneration (AMD) in a large French case–control population.

Patients and methods

One thousand and twenty-four patients with exudative AMD and 275 controls were recruited. Information about lifestyle, medical history, and dietary intake were collected. Associations of risk factors were estimated using logistic regression.

Results

After multivariate adjustment, CFH Y402H and ARMS2 A69S polymorphisms were associated with very high risk for exudative AMD (OR?=?6.21 and OR?=?11.7, respectively, p?<?0.0001). Risk for exudative AMD was increased in current smokers (OR?=?3.79, p?=?0.0003) and former smokers having quitted since less than 20 years ago (OR?=?2.30, p?=?0.002), but not in former smokers having quitted since 20 years or more ago (OR?=?0.81, p?=?0.43). Heavy smokers (at least 25 pack-years) were particularly at risk (OR?=?3.61, p?<?0.0001). Use of cooking oils rich in omega 3 fatty acids was significantly associated with a reduced risk of exudative AMD (OR?=?0.55, 95 % CI: 0.36–0.84, p?=?0.006), as well as a high consumption of fruits (OR?=?0.60, 95 % CI: 0.37–0.98, p?=?0.04), but not the consumption of fish, vegetables or oils rich in omega 6. High waist circumference was associated with increased risk for exudative AMD (OR?=?2.53, p?<?0.0001), but not hypercholesterolemia, hypertension, or body mass index.

Conclusions

The CAP Study confirms major genetic risk factors for exudative AMD. It further documents the high risk in heavy smokers and the long persistence of risk after smoking cessation, and the associations with waist circumference and fruit consumption. Furthermore, we observed an inverse correlation between AMD and cooking oils harboring a beneficial omega-3 fatty acid profile.     

A retrospective evaluation of the effect of hydroxyquinine on RPE thickness

Background

To investigate a possible structural difference in the retina of hydroxychloroquine (Plaquenil)-treated patients as an explanation for the protective effect of this medication against age-related macular degeneration (AMD).

Methods

In this retrospective study, we compared the mean thickness of the retinal outer band (consisting of the Bruch’s membrane and retinal pigment epithelium layer), as measured by optical coherence tomography (OCT), of 54 eyes of 27 hydroxychloroquine-treated rheumatoid arthritis patients (study group), 40 eyes of 20 healthy similar aged individuals (control group I), and 22 eyes of 11 non-hydroxychloroquine-treated rheumatoid arthritis patients (control group II).

Results

The mean thicknesses of the outer band of the retinal pigment epithelium layer was 60.4?±?7.4, 43.3?±?2.7, and 39.7?±?3.6 μm for the study group, control group I, and control group II, respectively. P values for differences in mean thicknesses were < 0.0001 between the study group and each of the control groups, and 0.086 between the two control groups.

Conclusion

Treatment with hydroxychloroquine was associated with increased thickness of the outer band of the retinal pigment epithelium layer. This finding may explain the protective effect of hydroxychloroquine against age-related macular degeneration (AMD).     

Novel automated screening of age-related macular degeneration

Purpose

To determine the objective and quantitative hyperspectral parameters for distinguishing between age-related macular degeneration (AMD) and a normal macula.

Methods

Near-infrared hyperspectral images were taken of 71 eyes of 62 AMD patients with exudative AMD and 21 eyes of 12 control subjects without AMD. The spatial information included a 480?×?321-pixel image in a 50° field located at the ocular fundus and a 720–950-nm-per-pixel reflectance spectrum. Macular vectors were determined as the average spectrum for each macula, and reference vectors were used as average macular vectors for healthy volunteers. Variations in vector length and angle were calculated based on comparison with the reference vector. The AMD differentiation index was a parameter that minimized the plot overlap between AMD patients and controls.

Results

Statistically significant differences between the AMD patients and controls were noted. Receiver-operating characteristic curve analysis revealed an area under the curve of 0.888. The appropriate threshold values were attained for the proposed discrimination index, including 68?% sensitivity, 95?% specificity and 74?% accuracy.

Conclusions

This study presents a simplified diagnostic index for the determination of age-related macular degeneration based on near-infrared spectra.     

Photodynamic therapy combined with intravitreal bevacizumab and sub-tenon triamcinolone acetonide injections for age-related macular degeneration

Purpose

To report the results of triple therapy with photodynamic therapy (PDT) (PDT combined with intravitreal injection of bevacizumab (IVB) and sub-tenon injection of triamcinolone acetonide (STTA)) for the treatment of age-related macular degeneration (AMD) in Japanese patients.

Methods

This retrospective case series included 38 eyes of 38 patients with exudative AMD treated with PDT combined with IVB (1.25 mg) and STTA (40 mg). Retreatment was performed in the same manner with intervals of at least 3 months. All patients had been treatment naïve, with a follow-up period of 12 months. Best-corrected visual acuity (BCVA), macular retinal thickness (MRT) on optical coherence tomography, and the number of treatments were analyzed.

Results

The mean logarithm of the minimum angle of resolution BCVA in patients treated with PDT triple therapy was 0.86 ± 0.55 at baseline and 0.62 ± 0.55 at 12 months (p < 0.001). The mean MRT was 554.0 ± 202.6 μm at baseline and 205.1 ± 78.6 μm at 12 months (p < 0.001). During the 1-year follow-up, the average number of PDT triple therapy (treatments per patient) was 1.1. No complications, for example increase in intraocular pressure, cataract, or endophthalmitis, were observed.

Conclusions

In AMD patients, PDT triple therapy significantly improved visual acuity with a minimum number of treatments and a low risk of complications during the 1-year follow-up.

     

Response to anti-VEGF therapy in patients with subretinal fluid and pigment epithelial detachment on spectral-domain optical coherence tomography

Purpose

To analyse the long-term functional and morphological response of a specific choroidal neovascular membrane (CNV) phenotype to anti-vascular endothelial growth factor (VEGF) therapy.

Methods

Data from 30 eyes of 30 consecutive patients with subretinal fluid (SRF) and fibrovascular pigment epithelial detachment (PED) due to CNV on spectral-domain optical coherence tomography (SDOCT) with a follow-up of at least 20 months were retrospectively collected. Main outcome measures included change in visual acuity, quantitative and qualitative parameters on SDOCT [photoreceptor layer, outer nuclear layer (ONL), choroid, PED, SRF] and on fluorescein angiography (CNV activity). Subjects were divided into responders and non-responders based on morphological and functional aspects.

Results

An average number of 20.23?±?9.9 anti-VEGF injections were administered during a mean follow-up of 40.25?±?13.5 months. Fourteen eyes were categorized as morphological non-responders, 12 as functional non-responders and eight as complete non-responders. Complete non-responders were significantly younger than complete responders (68.5?±?4.5 vs 74.3?±?6.8 years; p?<?0.05) and presented thinner baseline ONL values (68.43?±?15.2 vs103.5?±?32.8 μm; p?<?0.05). Intermediate or large drusen as typical features for age-related macular degeneration (AMD) were less frequently present in complete non-responders; however, this was not statistically significant (62.5 % vs 91.7 %; p?=?0.25).

Conclusions

Our preliminary findings indicate that eyes with the specific SDOCT phenotype with isolated fibrovascular PED and SRF frequently demonstrate non-response to anti-VEGF therapy, and the underlying disease mechanism may be different from AMD. Larger prospective trials are required to validate those results, and to develop strategies to improve the morphological as well as functional outcome.     

Multifocal pupillography identifies retinal dysfunction in early age-related macular degeneration

Background

Early age-related macular degeneration (AMD) is common among the elderly. While only a small number progress to sight-threatening stages of AMD, identifying prognostic functional markers remains paramount. Here, we objectively evaluate retinal function in patients with large drusen by multifocal pupillographic objective perimetry (mfPOP). Different temporal presentation rates and luminances were compared to optimize parameters for high signal to noise ratios (SNR) and diagnosticity for early AMD.

Methods

Pupil responses were recorded from 19 early AMD patients (30 eyes) and 29 age-matched control subjects. We compared a luminance-balanced stimulus ensemble and two unbalanced stimulus variants, each consisting of 44 independent stimulus regions per eye extending from fixation to 15? eccentricity. Video cameras recorded pupil responses for each eye under infrared illumination. The amplitudes and delays of the peak responses were analysed by multivariate linear models. The diagnostic accuracy of the stimulus variants was compared using areas under the curve (AUC) of receiver operator characteristic (ROC) plots.

Results

Early AMD eyes differed significantly from normal in their mean constriction amplitudes (?2.22?±?0.15 dB, t?=??14.8) and delays (17.92?±?1.2 ms, t?=?14.9). The brightest stimulus ensembles produced the highest median SNRs of 3.45 z-score units; however, the balanced method was found to be the most diagnostic. AUC values of 0.95?±?0.03 (mean ± SE) for early AMD were obtained when the asymmetry of response amplitudes between eyes was considered.

Conclusions

The mfPOP responses of early AMD eyes showed significant abnormality in response amplitudes and peak time. The ROC AUCs of 95 % suggest that mfPOP is a sensitive tool for detecting early abnormalities in AMD and longitudinal studies measuring progression of retinal dysfunction are warranted.     

Vascular Endothelial Growth Factor Inhibition bei altersbedingter Makuladegeneration: Einfluss von Rauchgewohnheiten auf den Behandlungserfolg

Background

To investigate the influence of smoking, age and systemic medication on the effectiveness of an anti-VEGF therapy in patients with exsudative age-related macular degeneration (AMD).

Patients and methods

A total of 100 patients were included in the retrospective analysis. Data included best-corrected visual acuity (BCVA) and number of injections in 24 months. Subjects with BCVA < 0.1 at baseline were rejected. All patients were interviewed about smoking habits and current systemic medication.

Results

The study comprised 42 smokers (including 31 past-smokers) with a median of 23.5 packyears (py). The more py a patient had smoked, the lower BCVA was after the last injection (p = 0.009). The more cigarettes per day a smoker had smoked the more injections he had received (p = 0.0042). Patients with arterial hypertension had a lower BCVA after the last injection (p = 0.045).

Conclusions

Smoking is not only a risk factor for the development of AMD but also for the effectiveness of an anti-VEGF treatment. Also from a socio-economic point of view AMD patients should be instructed to quit smoking.