Our findings show that ARMS2 A69S and CFH Y402H risk variants are significantly associated with RRD. We also found that ARMS2 A69S GT genotype has significant association with postoperative cystoid macular edema. RRD is a major cause of visual impairment and may be the result of the presence of retinal holes or tears. Although the only effective treatment modality of this disease is surgery, even successful operation fails to restore the normal visual capabilities because of functional alterations in the retina. Multiple inflammatory pathways have been shown to be activated after retinal detachment.17–18 Another study has shown early activation of inflammatory genes such as complement components genes in retinal detachment.13 This genetic expression alterations was also observed in the non-detached retina as well as in the underlying RPE layer.13
In this study we selected ARMS2 A69S and CFH Y402H as inflammatory polymorphic genetic loci to study their possible role in RRD susceptibility and its post-operative complication. ARMS2 (age-related maculopathy susceptibility) locus, originally named LOC387715, is located on Chromosome 10q26. Some have demonstrated a mitochondrial association of the ARMS2 protein and defined its retinal localization to the ellipsoid region of the photoreceptors.19 Others have reported its localization in the cytosol or extracellular matrix. 20–21
ARMS2’s role in the pro-inflammatory pathway has been shown by some authors.14,22−23 CFH Y402H (rs1061170) is located on Chromosome 1q32. Its polymorphism results in T to C change in exon 9 which causes tyrosine (Y) to histidine (H) exchange at position 402. CFH has an inhibitory effect on the alternative complement cascade and its polymorphism causes complement activation. The CFH Y402H polymorphism has been shown to increase the inflammatory milieu in the RPE/sub-retinal space.24–25 It has been suggested that ARMS2 and CFH Y402H genes have common pathway of effect because of synergistic interaction in AMD pathogenesis.14
In this study we found that among post-surgical RRD complications, cystoid macular edema is associated with ARMS2 A69S risk genotype. We could not find association of other complications such as macular atrophy, macular hole, redetachment, macular pucker, PVR or persistent SRF with studied genotypes. We observed strong association of ARMS2 A69S and CFH Y402H risk variants with RRD susceptibility. Apart from chronic RRD cases associated with atrophic holes, RRD is an acute disease which is dependent on fluid current through retinal break. We could not find any difference between RRD cases with HST and RRD cases with atrophic holes regarding these genetic loci polymorphisms. We speculate that these two genetic loci could have role in retinal break formation or their role in retinal/subretinal inflammatory milieu could affect neurosensory retinal attachment to RPE layer. In conclusion, this study showed strong association of ARMS2 A69S and CFH Y402H risk variants with RRD incidence and cystoid macular edema as its post-operative complication. We could not find any association between these genetic loci and other complications such as macular atrophy, macular hole, redetachment, macular pucker, PVR or persistent SRF. Limited number of cases and relatively short period of post- surgery follow-up are main limitation of this study. Future studies especially among RRD cases of chronic nature could clearly explain these genetic loci role in susceptibility to RRD and its complications.