Morphological and functional changes in spectral domain optical coherence tomography and microperimetry in macular microhole variants: spectral domain optical coherence tomography and microperimetry correlation.

PURPOSE: To evaluate the relationship between the morphology and retinal function of macular microhole (MMH) variants.
MATERIALS AND METHODS: We evaluated 12 eyes of 11 patients with defects in the IS/OS junction of photoreceptor layer with SD-OCT. All patients underwent comprehensive ophthalmic examination including spectral domain optical coherence tomography (SD-OCT) and microperimetry.
RESULTS: The mean logMAR visual acuity in the affected eye was 0.15 ± 0.17 (range 0.00-0.5). Mean horizontal diameter of the MMH was 163 ± 99 μm; the mean retinal sensitivity in the area corresponding to the MMH was 13.79 ± 4.6 dB. Negative correlation was found between the MMH diameter and the retinal sensitivity (r = -0.65, P = 0.02). Three morphological patterns of MMH variants were recognized on SD-OCT, which did not differ in retinal sensitivities.
CONCLUSION: We described and classified the MMH variants and made an assessment on the physiological functions using microperimeter.

Punctate foveal defects termed “microholes” have been described by Cairnes and McCombe,[1] as a minute red lamellar or full thickness defects, with size of <150 μm (using fundus photographs), occurring in the fovea – either uniocular or binocular. These lesions were smaller in size, associated with minimal visual deficits, and had a non-progressive clinical course.[2] Douglas et al, reported intraretinal red lesion, of unclear cause, described as a foveal spot.[3] The majority of patients with macular microhole had symptoms such as central scotoma, metamorphopsia, or reduced reading visual acuity, similar symptoms have been reported by patients having outer retinal defect involving the photoreceptors and/or retina pigment epithelium.[4] We report clinical findings of 12 eyes, with similar symptoms, whose structural and functional characteristics of intraretinal lesions were studied with spectral domain optical coherence tomography (SD-OCT) and microperimetry. This report is a first-of-its kind.

Materials and Methods

Twelve eyes of 11 patients with macular microhole (MMH) variants were included in this study. All patients underwent fundus examination, evaluation of vitreoretinal interface and retinal sensitivity using slit lamp biomicroscopy (Haag Streit DM 900, Switzerland and 78D volk lens), SD-OCT (SD-OCT, Copernicus, Poland), and microperimetry (MP1, Nidek, Padov). A detailed assessment of the symptoms, including the presence of scotoma, previous history of ocular trauma, direct sun light exposure, previous retinal disease, and use of retinotoxic drugs, was obtained. Informed consent was obtained from all subjects before they underwent the clinical examination.

Spectral domain optical coherence tomography

Retinal structural details in the MMH variants were obtained using SD-OCT (Copernicus, Poland). The SD-OCT system achieved data acquisition rates of up to 25,000 axial scans per second with an axial resolution of 6 μm. In the current study, 7 mm area of the macular region, centered on the fovea, was examined using the asterisk scan protocol with 6 B-scans and 2743 A-scans per B-scan with a total acquisition time of 0.6 s. A 7 × 7 mm area of the macular region, centered on the fovea, was examined with (3D image scan) 50 B-scans and 743 A-scans per B-scan with a total acquisition time of 1.5 s. The diameter of the MMH was measured using the calipers in SD-OCT. The maximum diameter of the lesion was considered for analysis.

Microperimeter (MP1)

On the same day, the retinal sensitivity in the area corresponding to the MMH was obtained using microperimeter (Nidek Technologies, Padua, Italy). Background illumination of the microperimeter was set at four apostilbs (1.27 cd/m2; 1 asb = 0.31831 cd/m2), stimuli intensity varied on 1 (0.1 log) step scale from 0 to 20 dB, where 0 dB represented the brightest luminance of 400 asb (127 cd/m2). Goldmann III Stimulus size was used. The fixation target size was adjusted according to the subject's visual acuity. Saccadic movements of the testing eyes were made at 25 times per second. This active tracking allowed the microperimeter to get reliable perimetry data even when the patient was unable to fixate. A false-positive test stimulus was projected every 60 s onto the optic nerve head area to check for a false-positive response. When the examination was complete, color photography was taken (1392 × 1038 pixels, xenon flash) and a registration technique was used to correlate the visual field data over the fundus photo. This made it easy to correlate the pathology with scotoma. For this study, we used a manual program, which was present in microperimeter; this program helped in stimulating the area of interest on the retina and the minimum distance between the stimuli was 0.1 [Fig. 1]. 4-2-1 staircase strategy was used.

Figure 1

Color fundus image of the right eye (a); the respective spectral domain optical coherence tomography scan (b); microperimetry in the region of macular microhole (c); the magnified microperimeter values at macular microhole area (d); demonstrated a well-demarcated defect (arrow) of the macular microhole variant structural changes of retinal layers as well as retinal sensitivity in respective area of defect

Statistical analysis

Data were analyzed with the help of SPSS (Statistical Package for Social Sciences) software version 14.0 (Chicago, Illinois). Spearman coefficient was used in the analysis of correlation among the different parameters, and the correlation coefficient was computed. A probability (p) value of ≤0.05 was considered significant.

Results

The mean age of the patients was 56.1 ± 15.4 years; there was no gender predilection; and the condition was unilateral except for one patient. None of the patients had a history of direct sun light exposure or a chronic use of drugs. Two of our study patients have complained of reduced vision since 6 months and one reported having metamorphopsia since 6 months and other having since 1 year. Seven patients did not present with any symptoms. The mean visual acuity was 0.15 ± 0.17 logMAR (range 0.00–0.5 logMAR). The mean spherical equivalent refractive error was -0.25 diopter (range +0.25 D to -3.50 D). The mean retinal sensitivity in the area of MMH was 13.79 ± 4.6 dB (range 6.7–19.7 dB) and the mean MMH diameter was 163 ± 99 μm (range 43–385 μm). A negative correlation was found between the MMH diameter and the retinal sensitivity (r = -0.65, p = 0.02). Fig. 2 shows the images of microperimetry performed in the area of MMH.

Figure 2

Microperimetry performed in the area of macular microhole

In our study, we looked into the status of the photoreceptor layer (PRL), the external limiting membrane (ELM), the retinal pigment epithelium (RPE), and the posterior vitreous separation. Loss of ELM was found in four eyes (33%). 6 of the 12 eyes (50%) had alterations at RPE. The results of vitreoretinal interface examination, using SD-OCT, were recorded for 11 patients, 4 (33%) of whom had posterior vitreous separation [Table 1]. Fig. 3 shows posterior vitreous detachment on SD-OCT images.

Table 1

Baseline patient characteristics

Figure 3

Spectral domain optical coherence tomography images showing posterior vitreous detachment

We found three distinct patterns of MMH variants in these patients [Fig. 4]:

Figure 4

Different patterns of macular microhole variants with spectral domain optical coherence tomography, (a) vertically placed rectangle; (b) straight triangle; (c) upright triangle

vertically placed rectangle which was observed in nine eyes (75%);

straight triangle which was observed in two eyes (16.6%);

upright triangle which was observed in one eye (8.3%).

Among the three patterns, we did not find any significant (p = 0.51) difference in the retinal sensitivity in the MMH area.

No significant (p = 0.90) difference of retinal sensitivity was found in the MMH area between the groups of patients who had both ELM and PRL loss and patients with only PRL loss. Similarly, no significant (p = 0.52) difference of retinal sensitivity in the MMH area was found between the group of patients with RPE and PRL loss and those with only PRL loss.

Discussion

In this study, we explained the morphological and functional characteristics of the MMH variants. These lesions were larger than the previously described MMHs.[145] The minimal loss of visual acuity, associated with MMH variants, was found to be less when compared to the loss of visual acuity in the MMHs.[2] Reduction of mean retinal sensitivity over the area of MMH was also noted. There was a significant negative correlation between the mean retinal sensitivity and the MMH diameter. The loss of retinal sensitivity could be because of the discontinuity of IS/OS junction of PRL.

With the help of 6 μm axial resolution of SD-OCT, in this study, we were able to identify the extension of the MMH from the ELM to the RPE layer, and discontinuity of inner and outer segment junctions of photoreceptors. We also measured the MMH diameter using measurement software on high-image quality scan. The MMH diameter in this study ranged from 43 to 385 μm. As in our study the MMH diameter was more than 150 μm in 4 out of the 12 patients (definition of MMH < 150 μm), and two of these patients presented macular holes larger than 300 μm, so we considered these as MMH variants.

In this study, we reported the morphology of MMH variants based on the observed patterns 1) vertically placed rectangle; 2) straight triangle; and 3) upright triangle. The vertically placed rectangle had the same apical and base diameter, the straight triangle had a base diameter greater than the apical diameter, and the upright triangle had a base diameter less than the apical diameter. There were no differences in retinal sensitivities in the three groups.

Vitreoretinal interface details were noted in the SD-OCT scan, 33% eyes (four eyes of 12) had posterior vitreous separation with no operculum. As previously reported,[5] microholes were likely to result from acute anteroposterior vitreous traction that either tore the center of the umbo or avulsed a small portion of the central fovea.

Zambarakji et al.,[4] described that MMHs are lesions in the outer retina, involving the photoreceptor segment and possibly the RPE. In this study, we found involvement of ELM, PRL, and RPE in the area of MMH. Lai et al.,[6] in their study on spontaneous resolution of MMH, have reported that the formation of MMH could be the result of resolving the full thickness macular hole. But none of our subjects had a history of ocular injury or previous history of vitreoretinal surgery. In this study, PRL discontinuity was found in all patients. Reduced retinal sensitivity at the area of MMH was probably due to the PRL loss.

Cause of MMH could be due to the developmental defect and there could be some genetical association, which can be assessed in future studies. And it has also been reported that in cases of parafoveal telangiectasia (PFT), there is a defect noted at the level of IS/OS junction of the photoreceptor.[7] So, this could be some variant of PFT.

In our study, we have performed SD-OCT and microperimetry on different instruments. But now with the help of OPKO spectral-domain OCT/SLO instrument (OPKO Instrumentations, Miami, FL, USA), which is a combination of OCT and confocal scanning ophthalmoscope , it is possible to perform simultaneous microperimetry and SD-OCT with which we can make sure that microperimetry and SD-OCT present exact the same area. This is an inherent limitation of our study.

From this study we hypothesize that the described MMH variants can be an intermediate stage between MMH and macular hole for which a longer follow-up and a larger sample-based study, which can give in-depth knowledge, are needed.