According to previous epidemiological investigations3 and clinical reports,12 IMH is much more common to occur in women than in men. This study enrolled a population with a female to male ratio of about 4:1, which is higher than that of previous epidemiological investigations,3 but comparable to other retrospective clinical reports concerning surgical patients.13,14 The data presented here reveal that IMHs of women seem to be larger and occur earlier than those of men, but there are no significant differences between genders concerning other pre-operative metrics and surgical outcomes.
In this study, the stage constituent ratio (stage3/stage4) of IMHs was significantly higher in women than in men. According to Gass’s classification system,9 the difference between IMH of the two stages is mainly the status of the vitreous at the optic disc, so that women owned more IMHs of stage 3 indicated the possibility that complete posterior vitreous detachment (PVD) occurs later in women than in men. The study of Schwab and colleagues observed 335 non-myopic eyes and found that women were significantly older than men when having the late-stage PVD (complete PVD) in the eyes,15 which was consistent with our speculation. This phenomenon could be explained by the findings of van Deemter and colleagues that female vitreous, especially after 50 years of age, experiences a faster accumulation of pentosidine,16 which is associated with the absence of a complete PVD.17
Kazuyuki et al. observed 526 eyes of 480 patients with stage 3 or stage 4 IMHs that had undergone vitrectomy, and found that females of stage 3 demonstrated younger age of onset and larger size of macular hole.18 Our results seem to be in agreement with this. However, the report of Kazuyuki et al.’s was not in English and the full text was not available online, so we cannot obtain any further details.
In high myopic eyes, macular holes occur earlier19 and evolve faster than in non-myopic eyes20 due to longer axial length20 and thinner retina thickness21 because these two factors may exacerbate the impact of traction forces on highly myopic eyes.22
In the present study, the foveal retina thickness of IMH eye before disease was unable to know owing to the hole, so CMT of the fellow eye was measured to represent. The results showed that AXL was longer and CMT was thicker in male than in female, which were in accordance with previous reports23,24 but seemed to be a contradiction concerning their opposite effects on development of macular holes. Meanwhile, CMT is positively related to AXL.24 Therefore, we introduced the concept of adjusted CMT calculated by CMT/AXL, regarding CMT and AXL as a whole, and found it significantly smaller in female than in male. This could probably explain why female exhibited younger age of onset in IMHs of stage 3. In other words, though developing stage 3 IMH earlier, women tend to remain in the same stage longer than men, and this also explains why IMHs of stage 4 showed no significant difference between genders in age of onset in our results.
With respect to morphological metrics, female IMHs exhibited larger MLD than male on the whole, which largely attribute to the difference in stage 3 IMHs. According to previous studies, MLD enlarges as the IMH progresses, while enlargement of BD slows down.25 Since female develop stage 3 IMHs earlier and stay in the same stage longer, it is reasonable that female IMHs of stage 3 are larger in MLD than male. As the disease evolves, difference of MLD became much less prominent between genders in stage 4 IMHs, which indicates that IMHs of both male and female evolve into a similar ultimate state.
The height of the hole was smaller in women than in men. Previous reports gave different conclusion on whether height of macular hole could predict surgical outcomes;26,27 however, their definition of the height - the greatest distance between the RPE layer and the vitreoretinal interface- differed from ours. In the present study, height of the hole was defined as the vertical height of the neuroepithelia edge starting from the junction point of the detached photoreceptor and the RPE, which we believe to be in accordance more with retinal thickness than retinal edema. In this regard, smaller H represents a relatively thinner foveal retina, which is consistent with the normal variation that CMT is smaller in women than in men.
Other derived indexes were calculated by MLD, BD, and H, so they showed understandable differences between genders in accordance with the three primary parameters.
According to previous studies, primary closure rate is mainly correlated with MLD and duration of symptoms, and post-operative BCVA with MLD and times of surgery.28 In this study, men and women showed similar primary closure rate and comparable highest BCVA during follow-up. That is to say, the differences between genders mentioned above may largely attribute to normal variations in foveal anatomy and physiology, but demonstrate limited influence on surgical outcomes; in other words, female IMHs may be not more severe than male as it may be anticipated. Males seem to recovery more quickly in post-operative BCVA, which is probably due to a smaller MLD and a thinner adjusted CMT, but whether there are causal correlations still needs further elucidation.
This retrospective study enrolled only patients who underwent operation, which may lead to a sample selection bias; however, the relatively large size of sample with rational gender proportion and rigorous methods could offer reliable results to a large extent. Usually, stage 2 IMHs are asymmetric in most scan directions because of the vitreomacular traction, which may lead to inaccuracy of parameter measurements like MLD and H. Thus, IMHs of stage 2 were excluded in this study.