Evaluation of Lamellar Macular Hole With Optical Coherence Tomography Angiography and Comparison Between Degenerative and Tractional Subtypes

doi:10.21203/rs.3.rs-996327/v1

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Evaluation of Lamellar Macular Hole With Optical Coherence Tomography Angiography and Comparison Between Degenerative and Tractional Subtypes

https://doi.org/10.21203/rs.3.rs-996327/v1

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Aim

To evaluate the optical coherence tomography angiography (OCTA) findings in cases with degenerative and tractional-subtype lamellar macular hole (LMH).

Methods

Two sub-types of LMH cases were included. Thirty-seven patients had degenerative-subtype, whereas 35 patients had tractional-subtype LMH. Thirty healthy cases were enrolled as control group. Foveal avascular zone (FAZ), retinal vascular densities in superficial, deep capillary and choriocapillaris plexuses were analyzed and compared with fellow eyes and healthy controls using OCTA.

Results

Mean FAZ area was wider in the degenerative-subtype (0.33±0.14 mm²) than the tractional-subtype (0.24±0.10 mm²) (p=0.04) and control eyes (0.26±0.10 mm²) (p=0.02). Compared with the tractional group, foveal vessel density in the superficial layer was lower in the degenerative group (29.1±6.9% vs.21.9±9.2%, p=0.01). Choriocapillaris vascular density in the parafoveal area was also lower in the degenerative-subtype lamellar macular holes ( 61.8±4.7% vs. 63.2±4.2 %) (p=0.03). The vascular densities in the DCP did not disclose any significant difference between two sub-types (p>0.05). Compared with control eyes, the vascular densities in the superficial, deep and choriocapillaris layers were significantly lower in the LMH subtypes (p<0.05).

Conclusion

These OCTA changes may indicate a primary or secondary chronic degenerative process affecting the retinal microvascular plexuses in degenerative and tractional lamellar macular holes. The distinction of the pathogenesis is also demonstrated by OCTA and supports the recent change in classification and terminology of this macular pathology.

Medical Genetics

Health Policy

Ophthalmology

Lamellar macular hole

optical coherence tomography angiography

foveal vascular density

degenerative sub-type

tractional sub-type

Lamellar macular holes (LMH) are defects of inner retinal layers, in which the outer retinal layers are protected. It was first described as a complication of cystoid macular edema after cataract surgery ¹. Optical coherence tomography (OCT) studies revealed an irregular foveal contour with intraretinal split, defect in inner retinal layers, and absence of a full-thickness foveal defect with intact foveal photoreceptors in these cases ^2,3. Two subtypes of LMH have been recognised: tractional LMH and degenerative LMH. Tractional type displays conventional epiretinal membranes (ERMs) with an intact ellipsoid layer and the degenerative type presents a schisis-like configuration, lamellar hole-associated epiretinal proliferation (LHEP) and often ellipsoid-layer disruption ⁴. Recently, the diagnostic criteria of LMH were defined based on the presence of irregular foveal contour, foveal cavity with undermined edges and loss of foveal tissue. According to the consensus; epiretinal proliferation, foveal bump or ellipsoid line disruption are accompanying pathological changes ⁵.

Optical coherence tomography angiography (OCTA) is a new high-resolution noninvasive technique that provides vascular network evaluation of ocular structures ^6,7. Recent studies using OCTA proposed microvascular changes of various retinal capillary plexuses in macular holes ^8–11. A significant controversy still exists regarding the pathogenesis, management and prognosis of lamellar macular holes. Indeed, data related to microenvironmental changes is limited.

In this study, we aimed to investigate characteristics of vascular parameters in degenerative and tractional-subtype lamellar macular holes and to compare with control subjects using OCTA and its software algorithms.

There were 18 females (49 %) and 19 males (51 %) in the degenerative group. In the tractional group were 19 females (54 %) and 16 males (46 %). Control group included 18 females (60%) and 12 males (40%). The mean age was 67.4±8.11 (range 55-81 years) and 71.7±6.97 (range 60-86 years) in the degenerative and tractional groups, respectively. The mean age in the control group was 66.1±6.05 (57-77 years). The age (p=0.851) and gender (p= 0.676) were similar in subjects and controls.

Degenerative-subtype LMH group included 37 eyes. The mean BCVA was 0.61±0.36 (1.3-0.1) logMAR in the degenerative group. The mean FAZ area was 0.332±0.14 mm² and was wider than fellow eyes (0.266±0.16 mm²⁾, which did not show statistically significance (p=0.06). Vascular densities in the perifoveal and parafoveal regions of the superficial capillary plexus were significantly lower than the fellow eyes (p=0.03) There were not significant difference regarding the vascular densities of the deep and choriocapillaris plexuses.

In the tractional group, there were 35 eyes with a mean BCVA of 0.58±0.43 (1.3-0.2) logMAR. The mean FAZ areas were 0.241±0.10 mm² and 0.203±0.11 mm² in the tractional group and fellow eyes, respectively (p=0.28). The foveal vascular density in the superficial capillary plexus was significantly higher (29.1 ±6.9%) than the fellow eyes (23.6 ±8.1%) (p=0.02). The vascular parameters in the superficial, deep, and choriocapillaris plexuses were comparable with the fellow eye vascular densities (Table 1).

Concerning the comparison between degenerative and tractional sub-types, the FAZ area was significantly wider in the degenerative group than the tractional group (p=0.04). Foveal vessel density in the SCP was lower in the degenerative group compared the tractional group (p=0.01). The vascular densities of the deep and choriocapillaris plexuses disclosed not a statistically significant difference between groups. The only exception was the reduced parafoveal vascular density of the choriocapillaris plexus in the degenerative group (p=0.03) (Table 2).

The comparison of the OCTA parameters between degenerative and tractional sub-types with control eyes are summarized in Table 3. The mean FAZ area was 0.26±0.10 mm²in the control group. Degenerative-subtype revealed significantly wider FAZ area than the control group (p=0.02) (Figure 1). The vascular densities in the superficial and choriocapillaris layers turned out to be significantly lower in the degenerative LMH eyes than the control eyes (p=0.001, p<0.001). The vascular densities in the deep capillary plexus was not different between groups, except the parafoveal area (p=0.02).

Regarding the comparison between tractional type LMH and control group, the mean FAZ area did not disclose statistically significance between groups (p=0.69). Foveal vessel density in the SCP was significantly higher in the tractional group than the control eyes (p<0.001). However, vascular densities in the superficial, deep and choriocapillaris layers were significantly lower compared to controls (p<0.05).

In the correlation analysis of two sub-types, the mean FAZ area was negatively correlated with the age in the tractional group (r=-0.51, p=0.02). According to the analysis, the foveal vessel density was positively correlated with the age (r=0.50, p=0.03). There was no correlation between VD parameters and BCVA in the tractional group. In the degenerative group, the correlation analysis did not show a significant relationship between vascular parameters and BCVA and the age (Figure 2 and 3).

In this study, we evaluated the eyes with LMH in two subtypes and compared with fellow eyes and healthy controls using OCTA. Our results emphasize superficial microvascular involvement in the degenerative and tractional groups compared to their fellow eyes. Furthermore, superficial, deep and choriocapillaris vascular densities in the LMH groups showed lower values than the control eyes.

Pierro et al. compared full thickness macular hole, LMH, macular pseudohole and healthy patients using OCTA and revealed vascular engorgement in especially DCP increasingly from LMH to the full thickness macular holes. In their study, they hypothesized that the alterations in SCP and DCP of unaffected fellow eyes may be a sign of early contribution to the development of macular holes ¹⁰. Although we did not find any difference between fellow eyes and tractional LMHs apart from the foveal vascular density, a decrease in SCP was found in degenerative LMHs compared to their fellow eyes.

Ahn et al. compared 19 eyes with LMH with normal controls and showed that the choriocapillaris vascular density was not different from the normal control group. They found an association between choriocapillaris flow and outer retinal integrity in full thickness macular hole cases, but not in LMH eyes ¹². In our study, decreased vascular densities were found in the superficial and choriocapillaris layers in both degenerative and tractional type LMHs compared to control eyes. In addition, vascular density in the DCP was decreased in the tractional group compared to the control eyes, and a decrease in the parafoveal area of the DCP was observed in the degenerative group. These findings may suggest an association of blood flow variation in the macular degeneration process.

Another study investigating the differences between degenerative LMHs and healthy eyes described a larger FAZ area and higher vascular density in the SCP as compared healthy eyes. Additionally, they found increased vascular density in unaffected fellow eyes ¹³. We found also larger FAZ area in degenerative group than healthy eyes. The larger FAZ area in the degenerative-subtype may be explained by the involvement of all retinal layers and may be considered a chronic degenerative process.

According to Govetto et al., the pathophysiological development mechanisms of the tractional and degenerative subtypes of LMH may differ from each other ¹⁴. In the tractional type, there is a schisis-like separation in the outer plexiform and outer nuclear layers secondary to traction, whereas in the degenerative type, there is a slow, chronic separation process involving all layers of the retina ^15,16. Also, Kashani et al. have described previously the reversible retinal vascular perfusion alteration due to the direct mechanical effect of vitreous traction in these cases ¹⁷. In the present study; the higher foveal vascular density in the tractional type may be explained by the tangential traction. Previous studies have also suggested that tractional forces induce microvascular changes and circulatory disturbances ^18,19.

Yeo et al. compared LMH in two subtypes with the control group and found FAZ area and foveal vascular density alterations both in tractional and degenerative subtypes ²⁰. The smaller FAZ area and higher foveal vascular density in the tractional group were similar to our results and was explained by the tangential traction mechanism as in the ERM. They found lower parafoveal vascular densities at the SCP and DCP in the degenerative group than those of the control group. In our comparison, we also found lower vascular densities in the degenerative group compared to the control eyes. On the other hand, the differences between the two subgroups suggest that the formation mechanisms of degenerative and tractional subgroups are different despite their clinical similarities.

The present study has several limitations. We studied a relatively small number of cases. Also, current study did not include patients who had macular surgery for LMH which could change the monitoring for microvascular changes.

Our results suggest that the macula in two subgroups of LMH shows differences in foveal hemodynamics. The different vascular features we determined in two different subtypes of LMH may be due to pathological changes associated with development process. There are limited data to demonstrate the macular capillary plexuses of eyes with LMH in two subtypes using OCTA.

In conclusion, the significant differences we revealed in the retinal microvasculature in degenerative and tractional LMHs may shed light on pathophysiologic mechanism. Also, these parameters may be used as a biomarker for disease progression. These results support the hypothesis of two distinct pathogenic formation for different subtypes. Larger studies observing retinal microvascularization and the alterations will further contribute to our clinical approach.

This cross-sectional observational study was performed at the Retina Department. The study followed the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of Ankara City Hospital (E1-20-318). All participants provided written informed consent.

All patients and control cases underwent an ophthalmic examination including best-corrected visual acuity (BCVA), anterior segment and fundus examination, tonometry, SS-OCT and OCTA imaging of the macula. The eyes with posterior segment disorders (e.g. retinal vein occlusion, optic neuropathy, uveitis), optical media opacities, previous laser or vitreoretinal surgery history, any intravitreal injection history or any macular pathology on OCT were excluded from the study.

SS-OCT and OCTA scans were obtained with RTVue-XR Avanti (Optovue, Inc., Fremont, CA) which has a high speed of 70,000 axial scans per second and axial resolution of 5-µm in tissue. This system uses split-spectrum amplitude decorrelation algorithm (SSADA) that provides intrinsic contrast with blood flow. The scan size was 6x6 mm of the macular area. The AngioAnalytic software analyzed the whole macular region into vascular networks of the retina: superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris plexus (CC). This software automatically calculated measurements of the FAZ area and retinal VD (vessel density) from selected layers of the retina that was defined as the percentage area of the vessels on the en-face scans.

The OCTA measurements of the vessel densities in the superficial, deep and choriocapillaris plexuses and FAZ areas were analyzed in degenerative and tractional sub-type LMHs and compared with their fellow eyes and healthy controls.

All variables were tested for normality assumption with Kolmogorov-Smirnov test of the SPSS Statistics software ver. 20 (IBM Corp., Armonk, NY). Differences between BCVA, FAZ area, vessel densities in retinal layers were assessed using one-way ANOVA test and Bonferroni correction as a posthoc test. P values less than 0.05 were considered statistically significant.

Acknowledgements

The authors are grateful to Prof. Defne Kalaycı for her valuable contribution and guidance.

Conflict of interest

None of the authors disclose financial interest.

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Due to technical limitations, table 1,2,3 is only available as a download in the Supplemental Files section.

No competing interests reported.

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Evaluation of Lamellar Macular Hole With Optical Coherence Tomography Angiography and Comparison Between Degenerative and Tractional Subtypes

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