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    Research update: 504

    The latest research highlights for 2 August 2021.

    Research update 504


    The Impact of Disease Activity on 5 year Outcomes in patients undergoing treatment for Neovascular Age Related Macular Degeneration.

    Retina. 2021 Jul 16.

    Chong Teo KY, Nguyen V, Gemmy Cheung CM, Arnold JJ, Chen FK, Barthelmes D, Gillies MC.

    PURPOSE: To assess the impact of disease activity on clinical outcomes in a “real-world” cohort with neovascular age related macular degeneration (nAMD) over 5 years.

    METHODS: Data were obtained from the prospectively-defined Fight Retinal Blindness! registry. Eyes were divided into tertiles based on the proportion of visits where choroidal neovascular lesion was active (low, moderate and high) up until 5 years.

    RESULTS: Data from 2109 eyes were included. The adjusted mean (95% CI) VA change was -0.5 letters (-1.8, 1.1), 1.8 letters (0.2, 3.4) and -2.5 letters (-4.2, -1.3) in the low, moderate and high activity groups respectively, p<0.001. Eyes in the low activity group were more likely to develop macular atrophy (56%, 47% and 26% in the low, moderate and high activity groups respectively, p<0.001) but less likely to develop subretinal fibrosis (27%, 35% and 42% in the low, moderate and high activity groups respectively, p<0.001).

    CONCLUSIONS: Eyes with higher and lower levels of disease activity had poorer outcomes than eyes with moderate activity over 5 years, apparently due to the development of subretinal fibrosis or macular atrophy.

    DOI: 10.1097/IAE.0000000000003267

    Effect of Residual Retinal Fluid on Visual Function in Ranibizumab-Treated Neovascular Age-Related Macular Degeneration: Effect of Retinal Fluid on Vision Outcomes in HARBOR.

    Am J Ophthalmol. 2021 Jul 18.

    Holekamp NM, Sadda S, Sarraf D, Guymer R, Hill L, Blotner S, Spicer G, Gune S.

    PURPOSE: To investigate the relationship between retinal fluid and vision in ranibizumab-treated patients with neovascular age-related macular degeneration (nAMD).

    DESIGN: Clinical cohort study using post hoc analysis of clinical trial data.

    METHODS: Setting: HARBOR (NCT00891735): phase III, randomized, controlled trial.

    POPULATION: 917 patients aged ≥50 years with subfoveal nAMD associated with subretinal (SRF) and/or intraretinal fluid (IRF) at baseline, screening, or week 1.

    INTERVENTION: Intravitreal ranibizumab 0.5 or 2.0 mg (all treatment arms pooled).

    OUTCOMES: Mean best-corrected visual acuity (BCVA) and BCVA change from baseline at months (M)12/24 evaluated by presence/absence of SRF and/or IRF.

    RESULTS: Baseline BCVA was higher with residual versus resolved SRF at M12 (mean [95% confidence interval (CI)], 58.8 letters [57.2 to 60.4] vs 53.5 [52.4 to 54.5]) and M24 (59.3 letters [57.8 to 60.8] vs 53.5 [52.5 to 54.5]). Mean BCVA change (adjusted for baseline) to M12 was greater with residual versus resolved SRF (mean difference [95% CI], +2.4 letters [+0.1 to +4.7]), but lower with residual versus resolved IRF (-3.5 letters [-5.8 to -1.2]). Eyes with residual SRF (no IRF) exhibited the largest mean BCVA gains (M12, +14.1 letters; M24, +13.2), followed by resolved SRF/IRF (M12, +10.6 letters; M24, +10.0), residual SRF/IRF (M12, +7.2 letters; M24, +8.5), and residual IRF only (M12, +5.5 letters; M24, +3.6).

    CONCLUSIONS: Vision outcomes (adjusted for baseline BCVA) through M24 were better in ranibizumab-treated eyes with residual versus resolved SRF, and worse with residual versus resolved IRF. Presence of residual retinal fluid requires a more complex and nuanced assessment and interpretation in the context of nAMD management.

    DOI: 10.1016/j.ajo.2021.06.029

    Macular thickness fluctuation in neovascular age-related macular degeneration treated with anti-vascular endothelial growth factor.

    Can J Ophthalmol. 2021 Jul 17.

    Chen ER, Chen AX, Greenlee TE, Conti TF, Briskin IN, Urbano CA, Kalur A, Kaiser PK, Singh RP.

    OBJECTIVE: To establish whether increased variability in macular thickness in neovascular age-related macular degeneration (nAMD) patients affects visual outcomes in clinical practice

    DESIGN: Retrospective cohort study

    PARTICIPANTS: Treatment-naive nAMD patients studied over 24 months METHODS: Central subfield thickness (CST) values from optical coherence tomography were collected quarterly from baseline to 24 months, and standard deviations (SDs) were calculated. The relationship was modeled with mixed-effects regression between CST SD and 24-month change in visual acuity (VA). Linear regression modeling determined predictors of CST SD.

    RESULTS: A total of 422 eyes with nAMD were studied. Baseline and 24-month CST values (mean ± SD) were 331.2 ± 97.6 and 253.4 ± 53.6 μm (Δ = -77.8 ± 104.7 μm, p < 0.001), with CST SD across 24 months of 42.0 ± 32.8 μm. Baseline and 24-month VA were 58.8 ± 19.2 and 62.4 ± 20.6 Early Treatment of Diabetic Retinopathy Study letters (Δ = +3.7 ± 20.8 letters, p = 0.008). CST SD over 24 months was a statistically significant negative predictor of 24-month change in VA (-15.41 [-20.98, -9.83] letters per 100 μm, p < 0.001). Quartile analysis of 24-month VA by CST SD showed a +11.2-letter difference between the first and last quartiles (p < 0.001). Baseline CST was a predictor of 24-month CST SD (24.88 [22.69, 27.06] μm per 100 μm, p < 0.001).

    CONCLUSIONS: Higher macular thickness fluctuations are related to poorer visual outcomes at 24 months in patients with nAMD treated with anti-vascular endothelial growth factor injections. Macular thickness variability may be an important prognostic factor of visual outcomes in nAMD eyes.

    DOI: 10.1016/j.jcjo.2021.06.004

    Relationship between retinal fluid and visual acuity in patients with exudative age-related macular degeneration treated with intravitreal aflibercept using a treat-and-extend regimen: subgroup and post-hoc analyses from the ALTAIR study.

    Graefes Arch Clin Exp Ophthalmol. 2021 Jul 20.

    Ohji M, Okada AA, Sasaki K, Moon SC, Machewitz T, Takahashi K; ALTAIR Investigators.

    PURPOSE: To explore the relationship between retinal fluid status and best-corrected visual acuity (BCVA) in patients treated with intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) in the ALTAIR study.

    METHODS: Outcomes were investigated according to overall fluid status at week 16 (predefined) and the relationship between any fluid, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment with BCVA at baseline, and weeks 16, 52, and 96 (post-hoc). The analyses involved treatment-naïve patients (N = 246) with exudative age-related macular degeneration (AMD), aged ≥ 50 years with BCVA of 73-25 Early Treatment Diabetic Retinopathy Study letters, who participated in the ALTAIR study.

    RESULTS: The mean (standard deviation) change in BCVA from baseline to week 52 was + 10.6 (10.9) and + 6.5 (16.0) letters in patients without and with fluid at week 16, respectively; and to week 96 was + 9.1 (14.3) and + 4.3 (16.1) letters in patients without and with fluid at week 16, respectively. The last injection interval was 16 weeks in 33.6% and 2.0% (week 52), and 62.9% and 17.6% (week 96) of patients without or with fluid at week 16, respectively. At baseline, 35.7% of patients had IRF and 85.2% of patients had SRF, which decreased to 11.8% (IRF) and 31.7% (SRF) of patients, 8.5% (IRF) and 18.7% (SRF), and 6.5% (IRF) and 20.7% (SRF) at weeks 16, 52, and 96, respectively. Presence of IRF at all timepoints was associated with poorer BCVA than if IRF was absent, while the presence of SRF was not associated with poorer BCVA compared with the absence of SRF.

    CONCLUSION: IVT-AFL T&E dosing was effective at clearing fluid regardless of fluid type in ~ 80% of patients with exudative AMD. Patients without fluid at week 16 had numerically better BCVA than those with fluid at week 16. Over 60% of patients without fluid at week 16 achieved the maximum treatment interval of 16 weeks by study end, compared with < 20% of patients with fluid at week 16. IRF (weeks 16, 52, 96), although evident in a small number of patients, was associated with poorer BCVA, whereas SRF was not.

    DOI: 10.1007/s00417-021-05293-y

    Multicentre, randomised clinical trial comparing intravitreal aflibercept monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) for the treatment of polypoidal choroidal vasculopathy.

    BMJ Open. 2021 Jul 15.

    Vyas CH, Cheung CMG, Tan C, Chee C, Wong K, Jordan-Yu JMN, Wong TY, Tan A, Fenner B, Sim S, Teo KYC.

    PURPOSE: To compare the efficacy and safety of intravitreal aflibercept (IVA) monotherapy versus aflibercept combined with reduced-fluence photodynamic therapy (RF-PDT) (IVA+RF-PDT) for the treatment of polypoidal choroidal vasculopathy (PCV). METHODS AND ANALYSIS: Multicentred, double-masked, randomised controlled trial to compare the two treatment modalities. The primary outcome of the study is to compare the 52-week visual outcome of IVA versus IVA+RF PDT. One hundred and sixty treatment-naïve patients with macular PCV confirmed on indocyanine green angiography will be recruited from three centres in Singapore. Eligible patients will be randomised (1:1 ratio) into one of the following groups: IVA monotherapy group-aflibercept monotherapy with sham photodynamic therapy (n=80); combination group-aflibercept with RF-PDT (n=80). Following baseline visit, all patients will be monitored at 4 weekly intervals during which disease activity will be assessed based on best-corrected visual acuity (BCVA), ophthalmic examination findings, optical coherence tomography (OCT) and angiography where indicated. Eyes that meet protocol-specified retreatment criteria will receive IVA and sham/RF-PDT according to their randomisation group. Primary endpoint will be assessed as change in BCVA at week 52 from baseline. Secondary endpoints will include anatomical changes based on OCT and dye angiography as well as safety assessment. Additionally, we will be collecting optical coherence tomography angiography data prospectively for exploratory analysis.

    ETHICS AND DISSEMINATION: This study will be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with the ICH E6 guidelines of Good Clinical Practice and the applicable regulatory requirements. Approval from the SingHealth Centralised Institutional Review Board has been sought prior to commencement of the study.

    DOI: 10.1136/bmjopen-2021-050252

    Intravitreal application of epidermal growth factor in non-exudative age-related macular degeneration.

    Br J Ophthalmol. 2021 Jul 14.

    Bikbov MM, Khalimov TA, Panda-Jonas S, Jonas JB.

    PURPOSE: To assess the safety of intravitreally applied epidermal growth factor (EGF). METHODS: The clinical interventional, prospective, single-centre, case series study included patients with age-related macular degeneration-related geographic atrophy (GA), in whom the eye with the worse best-corrected visual acuity (BCVA) underwent a single, or repeated, intravitreal injection of EGF (0.75 µg in 50 µL). At baseline and afterwards, the eyes underwent ophthalmological examinations.

    RESULTS: The study included seven patients (mean age:70.0±12.2 years (range: 54-86 years), with five patients receiving a single injection and two patients receiving two intravitreal injections in an interval of 4 weeks. Mean duration of follow-up was 97±97 days (median:35 days; range: 7-240 days). Mean BCVA was lower at baseline than at study end (1.41±0.44 logMAR vs 0.97±0.12 logMAR; p=0.03). Mean size of the GA lesions did not differ significantly between baseline and study end (29 212±22 887 pixels vs 29 300±22 905 pixels; p=0.59) nor did the mean perimetric mean defect (-10.3±5.9 dB vs 12.0±8.8 dB; p=0.35) or the electroretinographical b-wave amplitude (44.53±31.7 µV vs 64.5±25.5 µV; p=0.12). After a second injection 4 weeks after the first injection, one of two patients developed a cystoid macular oedema in association with an induced incomplete posterior vitreous detachment. It persisted for 3 weeks. Visual acuity in this eye improved from 1.0 logMAR at baseline to 0.80 logMAR at study end. CONCLUSIONS: Except for one eye with temporary, self-resolving cystoid macular oedema, single and repeated intravitreal applications of EGF (0.75 µg) in patients with GA did not lead to intraocular inflammations or any observed intraocular side effect.

    DOI: 10.1136/bjophthalmol-2021-319582

    Intravitreal air bubbles following intravitreal injections: a comprehensive analysis.

    Graefes Arch Clin Exp Ophthalmol. 2021 Jul 14.

    Krauthammer M, Trabelsi E, Moisseiev E.

    PURPOSE: To evaluate the prevalence of residual air bubbles following intravitreal injections of anti-VEGF agents, and to compare two techniques designed to reduce their occurrence.

    METHODS: Patients who received intravitreal injections reported the presence of air bubbles following the procedure, and were followed to determine when they disappeared. Two techniques used to reduce air bubbles prior to injection were compared-tapping the syringe with the needle up (“upwards” technique) or down (“downwards” technique). Rates of residual air bubbles were compared between techniques, and between different drugs.

    RESULTS: The study included 344 intravitreal injections, 172 injected with each technique. The overall rate of residual air bubbles was 11.3%, with 94.9% resolution by 48 h. The rate was significantly lower with the “downwards” technique (7.5% vs. 15.1%, p = 0.027). It was also significantly lower with ranibizumab injected using pre-filled syringes than with bevacizumab and aflibercept (0% vs. 12.1% and 14.7%, p < 0.0001). A questionnaire revealed patients reported medium levels of discomfort and a high importance of avoiding air bubbles.

    CONCLUSIONS: Residual air bubbles are a common occurrence, likely to be experienced by most patients undergoing repeated injections. This phenomenon may be significantly reduced by using the described “downwards” technique, or pre-filled syringes.

    DOI: 10.1007/s00417-021-05302-0


    Retro mode illumination for detecting and quantifying the area of geographic atrophy in non-neovascular age-related macular degeneration.

    Eye (Lond). 2021 Jul 14.

    Corradetti G, Byon I, Corvi F, Cozzi M, Staurenghi G, Sadda SR.

    PURPOSE: To evaluate the ability of retro mode illumination imaging for quantifying atrophy compared to confocal color fundus photography (c-CFP), green light fundus autofluorescence (G-FAF), blue light fundus autofluorescence (B-FAF) using the scanning laser ophthalmoscope (SLO) Mirante device by Nidek (Nidek Co., Ltd, Gamogori, Japan).

    METHODS: Eyes with clinical evidence of geographic atrophy (GA) associated with non-neovascular age-related macular degeneration, evaluated at the Doheny Eye Centers-UCLA and Hospital Sacco Milan, were included in this prospective, cross-sectional study. All eyes were imaged with multiple retinal imaging modalities using the SLO Nidek Mirante device: c-CFP, G-FAF, B-FAF, retro mode illumination deviated-right (RMDR), and deviated-left (RMDL). Masked graders measured the GA lesion on each modality and inter-modality and inter-grader repeatability were assessed.

    RESULTS: The mean (SD) area of GA measured 9.76 (3.82) mm2, 9.75 (3.91) mm2, 9.76 (3.92) mm2, 9.82 (3.87) mm2, and 9.81 (3.86) mm2 using c-CFP, G-FAF, B-FAF, RMDR, and RMDL, respectively (p = 0.2). Inter-modality correlation was high (Pearson’s r > 0.9 and p < 0.0001). Agreement between graders was excellent for all modalities.

    CONCLUSIONS: Retro mode imaging demonstrated good agreement for measuring GA compared to other imaging modalities, with a high level of repeatability. Given that retro mode imaging uses infrared light and is comfortable, it may prove to be a useful tool for the assessment of GA in the clinic.

    DOI: 10.1038/s41433-021-01670-3

    Outer retinal tubulation formation and clinical course of advanced age-related macular degeneration.

    Sci Rep. 2021 Jul 19.

    Arrigo A, Aragona E, Battaglia O, Saladino A, Amato A, Borghesan F, Pina A, Calcagno F, Hassan Farah R, Bandello F, Battaglia Parodi M.

    Outer retinal tubulations (ORT) are a relatively new finding characterizing outer retinal atrophy. The main aim of the present study was to describe ORT development in advanced age-related macular degeneration (AMD) and to assess its relationship with disease’s severity. Patients with advanced AMD characterized either by macular neovascularization or geographic atrophy, showing signs of outer retinal disruption or retinal pigment epithelium atrophy on structural optical coherence tomography (OCT) at the inclusion examination were prospectively recruited. All the patients underwent complete ophthalmologic evaluation, structural OCT scans and fundus autofluorescence imaging. The planned follow-up was of 3-years. Main outcome measures were ORT prevalence, mechanism of ORT formation, mean time needed for complete ORT formation, best-corrected visual acuity (BCVA), definitely decreased autofluorescence (DDAF) area, questionably decreased autofluorescence (QDAF) area, retinal layer thickness, foveal sparing, number of intravitreal injections. We also assessed the possible role of external limiting membrane (ELM) and Müller cells in ORT pathogenesis. Seventy eyes (70 patients) were included; 43 showed dry AMD evolving to geographic atrophy, while 27 displayed the features of wet AMD. Baseline BCVA was 0.5 ± 0.5 LogMAR, decreasing to 0.9 ± 0.5 LogMAR at the 3-year follow-up (p < 0.01). We detected completely formed ORT in 26/70 eyes (37%), subdivided as follows: 20 eyes (77%) wet AMD and 6 eyes (23%) dry AMD (p < 0.01). ORT took 18 ± 8 months (range 3-35 months) to develop fully. We described the steps leading to ORT development, characterized by progressive involvement of, and damage to the photoreceptors, the ELM and the RPE. Eyes displaying ORT were associated with a smaller QDAF area, less retinal layers damage and lower rate of foveal sparing than eyes free of ORT (p < 0.01). We also described pigment accumulations simulating ORT, which were detected in 16/70 eyes (23%), associated with a greater loss of foveal sparing, increased DDAF area and smaller QDAF area at the 3-year follow-up (p < 0.01). In conclusion, this study provided a description of the steps leading to ORT development in AMD. ELM and Müller cells showed a role in ORT pathogenesis. Furthermore, we described a subtype of pigment hypertrophy mimicking ORT, evaluating its clinical utility.

    DOI: 10.1038/s41598-021-94310-5


    KSI-301: antibody biopolymer conjugate in retinal disorders.

    Ther Adv Ophthalmol. 2021 Jul 12.

    Chandrasekaran PR, Madanagopalan VG.

    KSI-301 is a new intravitreal anti-vascular endothelial growth factor (VEGF) antibody biopolymer conjugate under investigation for the treatment of age-related macular degeneration (AMD), diabetic macular oedema (DME) and retinal vein occlusion (RVO). Preclinical and early clinical trials so far have shown promising results in retinal vascular diseases. When using anti-VEGF agents for treatment of retinal disorders, the frequency of injections and follow-up visits has increased the treatment burden, greatly affecting the treatment outcome. There are new anti-VEGF agents in the horizon with extended duration of action, durability, safety profile and efficacy, which seem to address the above issues. PubMed search and Medline search were performed on newer anti-VEGF agents, KSI-301, antibody biopolymer conjugate in retina, KODIAK KSI-301, DAZZLE study, GLEAM study, GLIMMER study, GLOW study and BEACON study. This review article showcases the biophysical properties and ongoing trials related to KSI-301. Moreover, we discuss the efficacy and safety profile of KSI-301 on the basis of the results of available trials.

    DOI: 10.1177/25158414211027708


    Vitrectomy in full thickness macular holes on top of a pigment epithelial detachment in age-related macular degeneration (AMD). Surgical consideration and review of the literature.

    Am J Ophthalmol Case Rep. 2021 Jul 10.

    Meyer PS, Kammann MT, Meyer CH

    PURPOSE: To present the surgical treatment of a full thickness macular hole (MH) caused by a vitreomacular traction (VMT) on top of an adjacent subfoveal pigment epithelial detachment (PED) in age-related macular degeneration (AMD).

    OBSERVATION: A 77-year-old female with a subfoveal PED receiving consecutive intravitreal injections noticed a sudden decreased visual acuity (VA) due to the development an occult MH in her right eye after 19 repeated intravitreal anti vascular endothelial growth factor (VEGF)-injections. Her initial VA declined from 20/50 to 20/400. The firm VMT induced a rupture of the multi-layered retina and may progress to an RPE-tear or possible to a subretinal haemorrhage. We discussed with the patient the risks of the natural progression and explained possible treatment options: We continued her anti-VEGF combined with air bubble injections to induce a posterior vitreous detachment, to stabilise the retinal architecture, reduce the subretinal fluid and avoid possible intraoperative bleeding. As injections did release the VMT, vitrectomy released the posterior vitreous from the optic nerve and trimmed it towards the central retina. Peeling with brilliant blue removed the internal limiting membrane without any signs of bleeding, rupture of the PED or enlargement of the MH, prior to the installation of 10% SF6 gas. The postoperative optical coherence tomography (OCT) on day 5 confirmed a closed MH, while the size, shape and pattern of the PED remained unchanged. Her VA increased from 20/400 to 20/50 (equal to her previous VA prior to the MH-formation). To avoid a potential progression of the PED, we maintained her retreatment intervals at 5 weeks for the next 6 months. A literature review presents similar intraoperative approaches and postoperative outcomes in 8 out of the 9 published cases.

    CONCLUSIONS AND IMPORTANCE: VMT can induce an occult MH on top of a PED, causing a significant loss of vision. When gas injections are not successful, surgery may release the traction, restore the retinal architecture, and significantly improve and maintain the VA over a documented long-term observation. The epiretinal procedure should be assisted under regular anti-VEGF injections to maintain the subretinal architecture.

    DOI: 10.1016/j.ajoc.2021.101154

    Regression of taxane-related cystoid macular edema after topical dorzolamide treatment: two case reports.

    J Med Case Rep. 2021 Jul 21.

    Otsubo M, Kinouchi R, Kamiya T, Yoshida A.

    BACKGROUND: Cystoid macular edema is a rare, vision-threatening side effect of the taxane family of anticancer agents. There is no established treatment or standard treatment protocol for taxane-related cystoid macular edema. Here, we report two cases of taxane-related cystoid macular edema that were treated with topical dorzolamide.

    CASE PRESENTATION: In case 1, a 72-year-old Japanese woman with bilateral geographic choroiditis reported for a follow-up visit with a complaint of blurred vision in both eyes for 2 months after starting nanoparticle albumin-bound paclitaxel chemotherapy for multiple metastases of her breast cancer. Her best-corrected visual acuity had dropped from 1.2 to 0.9 in the right eye and from 1.0 to 0.4 in the left eye. Fundus examination showed no newly active geographic choroiditis lesion, but optical coherence tomography exhibited cystoid macular edema. We suspected taxane-related cystoid macular edema and terminated nanoparticle albumin-bound paclitaxel, and started topical dorzolamide treatment. Cystoid macular edema nearly resolved within 6 weeks in the right eye and within 10 weeks in the left eye after starting topical dorzolamide treatment. The resolution of cystoid macular edema without leaving a chorioretinal scar after discontinuation of paclitaxel confirmed our initial diagnosis of taxane-related cystoid macular edema. A few inconspicuous cystoid spaces persisted at the parafovea for a year after dorzolamide treatment ended, but regressed after restarting dorzolamide treatment without any side effects. Best-corrected visual acuity improved to 1.2 in the right eye and 1.0 in the left eye. In case 2, a 70-year-old Japanese man, who received nanoparticle albumin-bound paclitaxel for pancreatic cancer with multiple metastases, developed bilateral cystoid macular edema. Best-corrected visual acuity was 0.3 bilaterally. Cystoid macular edema resolved within 5 weeks after stopping nanoparticle albumin-bound paclitaxel and starting topical dorzolamide treatment confirming the diagnosis of taxane-related cystoid macular edema. Nine weeks later, best-corrected visual acuity improved to 0.8 in the right eye and 1.0 in the left eye.

    CONCLUSIONS: Cystoid macular edema in each case resolved within a few months without any side effects using topical dorzolamide and terminating taxane-based chemotherapy. Topical dorzolamide appears to be a safe and effective treatment option for patients with taxane-related cystoid macular edema whose quality of life is threatened by visual disturbances.

    DOI: 10.1186/s13256-021-02954-8


    Associations of TLR4 and IL-8 genes polymorphisms with age-related macular degeneration (AMD): a systematic review and meta-analysis.

    Ophthalmic Genet. 2021 Jul 21:1-9.

    Roshanipour N, Shahriyari E, Ghaffari Laleh M, Vahedi L, Mirjand Gerami S, Khamaneh A.

    BACKGROUND: The results of different studies have indicated the possible associations of TLR4 and IL-8 genes polymorphisms with Age-related Macular Degeneration (AMD). A meta-analysis study was designed to evaluate the possible associations of TLR4 (rs4986790/c.896A>G and rs4986791/ c.1196 C > T) and IL-8 (rs4073/c.251A>T and rs2227306/c.781 C > T) genes polymorphisms with AMD.

    METHOD: A systematic literature search was carried out in PubMed, Embase, Web of Science, and Scopus databases to identify relevant publications. Pooled Odds Ratio (OR) with 95% Confidence Interval (CI) was used to evaluate the power of association.

    RESULTS: A total of 12 case-control studies with 4804 AMD patients and 4422 healthy controls were included in this meta-analysis. The analysis of genotypic and allelic models demonstrated significant associations between IL-8 c.781 C > T (CC vs. TT+TC: OR = 0.62 [0.48-0.81], P < .01; CC vs. TC: OR = 0.65 [0.48-0.89], P < .01; TT vs. CC: OR = 1.64 [1.04-2.57], P = .03; and C vs. T: OR = 0.71 [0.65-0.79], P < .01) and risk of AMD, which all of them passed Bonferroni correction for multiple testing (P-value≤0.01), except for TT vs. CC model. In addition, we found associations under the genotypic model of TLR4 c.896A>G (AA vs. AG+GG: OR = 0.73 [0.55-0.97], P = .03; and AA vs. AG: OR = 0.71 [0.53-0.95], P = .02) although after Bonferroni correction (P’-value<0.02) none of these associations remained significant. However, the data from this meta-analysis declined the associations of TLR4 c.1196 C > T and IL-8 c.251A>T polymorphisms with AMD.

    CONCLUSION: The current meta-analysis study suggested that IL-8 c.781 C > T polymorphism is associated with susceptibility to AMD.

    DOI: 10.1080/13816810.2021.1955274