Our study found that 58/147 eyes (39.5%) with MTM progressed over the 2-year follow-up period, and eyes with retinoschisis prominently located in the fovea or posterior staphyloma were prone to progression. Vitreoretinal traction may be one of the risk factors for progression, and the integrity of the EZ was considered to be a main factor affecting visual prognosis.
The progression rate of MTM or retinoschisis varies, ranging between 11.6% and 68.9%, according to different standards14,15. Gaucher et al14 found that 68.9% (20/29 eyes) of the eyes with foveoschsis progressed with enlargement of retinal cleavage and/or visual decline during a mean follow-up period of 31.2 months. In our retrospective study, 48/123 eyes (39.0%) with MTM progressed based on the criteria of morphological changes of MTM described by Shimada et al15, even when 24 S0 eyes were excluded at baseline, which was much higher than that reported by Shimada et al15 (11.6%). The different progression rates may be related to the difference in age, the status of vitreomacular traction, the involved location and area of schisis or the follow-up period in these studies.
Our results showed that eyes with outer schisis prominently located in the fovea or posterior staphyloma had a higher risk of progression than those in which outer schisis was located in the vascular areas. The mechanism of retinoschisis is complicated, and the growth of the eyeball is considered an initial factor in the pathogenesis of foveoschisis18. Shinohara et al19 suggested that posterior staphyloma may act as the main cause of retinoschisis located within the area of the posterior staphyloma by ultrawide-field swept-source OCT, and outer and inner retinoschisis located in vascular arcades may be caused mainly by vitreous adhesion in the blood vessels of the retina and the tractional force of the retinal arterioles20. However, after reaching the loose outer retina through the transmission of intraretinal tissues, the inner traction may become weak, and the inner retina may play a “shock-absorbing”-like role, while outward traction is direct and persistent, which may be the reason why outer retinoschisis at the blood vessel develops more slowly than that in the fovea. In our series, almost all cases of inner schisis were confined to the paravascular area adjacent to the superior or inferior temporal vascular arcades, which may result from tangential traction of the retinal arterioles. The presence of inner schisis did not significantly promote the progression of outer schisis in different locations regardless of the presence of ILM detachment, revealing that the retina itself may play a secondary role in the occurrence and development of outer schisis. In this study, MTM with partial PVD during follow-up was more likely to progress. Shinohara et al19 also proposed that the posterior vitreous extensively adhered to the retinal surface, exerting persistent inward traction in eyes of retinoschisis, which may contribute to the development of retinoschisis without posterior staphyloma. Additionally, we found that the stage of schisis had no significant influence on the risk of progression. Shimada et al15 and Cheng et al16 suggested that the status of S4 eyes was unstable and had a high risk for deterioration. Cai et al12 also believed that as long as the schisis involved the fovea, regardless of whether it extended to the entire macula, the possibility of progression was relatively high. Therefore, attention should be paid to each stage of MTM, especially in eyes with vitreomacular adhesion, and appropriate interventions should be given before MTM develops. Meanwhile, we observed that eyes in which ILM detachment was disrupted or disappeared did not progress. In foveoschisis, Müller cells and astrocytes proliferate to produce tangential stress to separate the intraretinal tissues10. Once ILM detachment is disrupted, tangential stress is released, and the splitting cavity may shrink or even completely disappear.
In this study, patients who were older than 65 years ,who had EZ defects at the first visit had poor final BCVA, and further multiple linear regression analysis showed that first-visit visual acuity and EZ defects are factors affecting visual prognosis. The interruption or absence of reflection EZ in the outer retina of retinoschisis may represent the abnormal energy metabolism of the elongated mitochondria of the photoreceptors, which means that visual function is impaired. Damage to EZ is not uncommon in patients with retinoschisis. Sayanagi et al21,22 reported that the incidence of EZ defects in foveoschisis is between 29% and 38%. Studies on the influencing factors of vision recovery after vitrectomy for foveoschisis have confirmed that the recovery of the EZ has a significant correlation with postoperative vision recovery23,24. Cheng et al16 reported that 6/14 (42.9%) patients with retinoschisis who had ≥ 2 lines of vision loss in their natural courses had EZ disruption at the first visit. We speculate that some elderly patients had a long course of schisis, and the baseline EZ was not intact or even absent, the photoreceptors were damaged severely over time, which subsequently caused poor vision. Even in pseudophakic eyes, the improvement in their visual function was not satisfactory after cataract surgery.
Our study has some limitations. First, the occurrence and development of cataracts in some elderly patients who experienced a long follow-up time inevitably affected visual acuity, and an electrophysiological examination may be required as a good supplement to evaluate visual function and prognosis. Second, the exertion of centrifugal vertical and tangential forces may cause an increase in the height and expansion of the extent of retinoschisis, respectively. In future studies, if we can increase the sample size, quantify the extent of the schisis, supplement the criteria for the progression of MTM, and further explore the equivalence of the impact of the expansion of the extent and the increase in height of the schisis on the progression of MTM, it may be of some significance to investigate its pathogenesis.
In summary, MTM had a high progression rate during the follow-up. MTM progression was related to the location of retinoschisis. Vitreomacular traction may play an important role in the natural course of MTM. Defects in the EZ have a negative influence on visual prognosis. MTM with schisis prominent in the fovea or posterior staphyloma and with obvious vitreomacular traction should be regularly followed, morphological changes in the outer retina should be considered, and surgical intervention should be carried out once the disease worsens.