Взаимосвязь между сохранностью фовеальных фоторецепторов и остротой зрения в конечном исходе неоваскулярной возрастной макулярной дегенерации

Age-related macular degeneration (AMD) is a significant source of vision impairment in older adults and is the leading cause of vision loss and blindness among individuals over the age of 60 years in industrialized countries [1, 2]. Anti-angiogenic (anti-vascular endothelial growth factor, anti-VEGF) therapy, photodynamic therapy (PDT), and angiostatic steroid therapy are commonly used treatments for exudative changes caused by choroidal neovascularization (CNV) secondary to neovascular AMD (nAMD) [3]. These therapies can help resolve exudative changes and improve visual acuity [1, 4, 5].

Regardless of the resolution of fluid accumulation, some subjects with nAMD still experience poor vision [6]. A study by Moutray et al. found that the thickness of the retina does not always correspond with visual function in nAMD [7]. Spectral domain optical coherence tomography (SD-OCT) features improved axial resolution over conventional time-domain OCT, allowing for a clearer view of intraretinal microstructures such as the photoreceptor inner segment/outer segment (IS/OS) junction and the external limiting membrane (ELM) [8]. Previous research have demonstrated a strong association between the preservation of the photoreceptor IS/OS junction and visual function in a variety of retinal conditions, including central serous chorioretinopathy and retinal vein occlusion. It is widely accepted that the presence of the photoreceptor IS/OS junction line and the ELM indicate the intactness of the foveal photoreceptor layer. However, earlier studies have generally centered on the integrity of the foveal photoreceptors, leaving limited evidence on other variations in retinal structure [9—11]. In the present study we used SD-OCT images to evaluate the impact of various foveal microstructures, such as the ELM, size of the CNV, central macular thickness (CMT), outer nuclear layer (ONL) thickness, and retinal pigment epithelium (RPE), on visual outcomes in patients with nAMD before and after treatment. The integrity of the foveal photoreceptor layer was assessed using the presence of the photoreceptor IS/OS junction line as a marker. The purpose of the present study was to identify factors that could predict and explain final visual acuity in the treatment of nAMD.

This study was conducted at the Institute of Ophthalmology, at Liaquat University of Medical & Health Sciences (LUMHS) Jamshoro, Pakistan, analyzed 80 patients with nAMD. The subjects received successful treatment through anti-VEGF injections. In this study, every patient has undergone a comprehensive ophthalmic examination including intraocular pressure, fundus photography, slit-lamp biomicroscopy, best-corrected visual acuity, and fluorescein angiography. SD-OCT was performed at the beginning of the study and repeatedly during the follow-up period to monitor alterations in exudation and assess the integrity of the IS/OS junction. This imaging test uses light waves to produce precise cross-sectional images of the retina.

This study excluded patients with CNV originating from other sources, such as persistent fluid accumulation at the last examination, intense inflammation of the uvea, and vitreous hemorrhage. Additionally, this study also excluded patients who had undergone prior laser treatment or those who had concurrent ocular conditions such as proliferative diabetic retinopathy, epiretinal membrane, or glaucoma. At the final visit, the subjects were classified into three groups using SD-OCT. Group 1 had a fully visible IS/OS junction, group 2 showed a partially visible IS/OS junction, and in group 3 the IS/OS junction line was not visible on the SD-OCT images. The measurement of the following parameters was performed at the initial and final visits: length of the disrupted IS/OS junction line, central macular thickness, size of choroidal neovascularization and ELM. In addition, RPE integrity and ONL thickness were evaluated at the final visit.

Total of eighty patients (49 males and 31 females) were studied. The distribution of gender among the three groups is depicted in Fig. 1. The subjects’ age spanned from 54 to 78 years, with mean age of 68.86±7.48 years, as depicted in Fig. 2. At the first visit, all subjects’ eyes showed substantial exudative changes related to nAMD. It was observed that the mean CMT was 411.44±146.3 µm, and the mean BCVA (logMAR) was 0.703±0.23. In this study, the IS/OS junction line was completely preserved in 15 out of 80 eyes (18.75%) on SD-OCT scans after anti-VEGF injections, in 29 eyes (36.25%) it was partially visible, and in 36 eyes (45%) the IS/OS line was not visible within 500 µm of the foveal center. At the final visit, the average thickness of the ONL was 59.96 µm in the group with fully preserved IS/OS junction (group 1), 49.56 µm in the group with IS/OS junciton partially visibile (group 2), and 56.75 µm in the group with IS/OS junction not visibile (group 3). The difference in ONL thickness among the groups was non-significant (p=0.221). Clinical characteristics and treatment outcomes with neovascular AMD among three groups with its p-value are shown in the Table.

Fig. 1. Gender distribution of nAMD patients included in the study

Fig. 2. Age distribution of nAMD patients included in the study

Clinical characteristics and outcomes of nAMD

In this study, the SD-OCT scans were used to assess the status of the RPE beneath the fovea. In 23 out of 80 eyes (28.75%) the RPE line was smooth and regular, while in 57 eyes (71.25%) it appeared undulated and irregular. Based on the status of the RPE, the difference in final visual acuity (measured in logMAR) between the two groups was not statistically significant. The average visual acuity was 0.75 in the group with a regular RPE, and 0.49 in the group with an irregular RPE. Fig. 3 demonstrates the statistically insignificant difference among the study groups (p=0.129).

Fig. 3. Distribution of eyes according to the status of retinal pigment epithelium.

The present study discovered a correlation between improvement of exudative change through anti-VEGF treatment and visual acuity. Results showed that a better final visual acuity was achieved when the IS/OS junction line was located beneath the fovea. Predictors of intact photoreceptor integrity after treatment included better initial visual acuity, thinner CMT, ELM, smaller CNV height, and shorter initial length of disrupted IS/OS junction line. However, after the treatment, the regularity of the RPE, CMT, and final ONL thickness had a non-significant correlation with photoreceptor integrity. Our findings support the findings of earlier studies that suggest a connection between the integrity of the photoreceptor layer in the fovea and visual outcomes in patients with nAMD after receiving PDT or anti-VEGF treatment [12, 13]. Hayashi et al. found in their study of 51 eyes treated for nAMD with PDT, that the IS/OS junction line was completely visible (15.7%) or partially visible (29.4%) under the fovea, while the IS/OS junction line was invisible in 54.9% eyes [14]. Compared to Hayashi et al.’s results, the present study exhibited a relatively more percentage of intact IS/OS junction (17.5% completely visible, 37.5% partially visible and 45% invisible). This difference might indicate that anti-VEGF treatment is more effective at preserving or restoring photoreceptor integrity compared to PDT [14]. Chang et al. found no association between visual acuity improvement and change in IS/OS defect size after macular hole surgery [15]. However, Hayashi et al. reported a strong association between the integrity of the foveal IS/OS and final visual acuity in nAMD after successful PDT [14]. These results indicate that the relationship between photoreceptor integrity and the visual outcomes may vary based on the specific condition being treated. Sayanagi et al. also found a correlation between the status of the IS/OS junction after anti-VEGF therapy, and both BCVA and the mean change in BCVA [16]. These findings support the idea that photoreceptor integrity is an important factor in determining visual outcomes after anti-VEGF treatment for nAMD. To summarize, this work demonstrates that SD-OCT offers comprehensive evidence about the integrity of the foveal photoreceptor layer both before and after treatment for nAMD. The study showed that photoreceptor integrity is closely linked to final visual acuity in patients with nAMD after treatment. The factors predicting final photoreceptor integrity include initial visual acuity, the initial length of disrupted IS/OS junction line, CMT, ELM, and CNV height.