Metamorphopsia Assessment before and after Vitrectomy for Macular Hole

Abstract

Purpose.: To evaluate the degree of metamorphopsia in 42 patients before and 6 months after vitrectomy for idiopathic unilateral macular hole.

Methods.: Semicircular test and reference stimuli of variable diameters were applied in a binocular test that measured interocular size disparity in patients with unilateral macular hole. The test was applied 1 day before surgery and repeated after 6 months.

Results.: Before surgery, mean disparity was 0.34° at 1° visual field eccentricity declining to a plateau value of approximately 0.2° between 3° and 5° of eccentricity. Six months after successful hole closure, interocular disparity was practically constant, with a median disparity below 0.1 and no significant effect of eccentricity. Baseline interocular disparities lower than 0.35° at 1° eccentricity were associated with nine EDTRS letters of better visual outcome compared with higher disparities (P < 0.001).

Conclusions.: Metamorphopsia was consistently reduced after macular hole surgery, supporting that the intervention was successful in repositioning displaced photoreceptors toward their original location. Final best corrected visual acuity was related to the degree of preoperative disparity in spatial projection between receptive units with a shared perceptual projection in visual space in the two eyes. (ClinicalTrials.gov number, NCT00302328.)

Visuospatial distortion, metamorphopsia, and reduced visual acuity are features of retinal diseases that distort the photoreceptor mosaic. During the formation of an idiopathic macular hole, a localized circular displacement toward a more peripheral location occurs around a point in or near the center of the foveola, the pattern of displacement being a regular and circular one. ¹ The hole appears to form spontaneously, and the condition predominantly affects women above the age of 60. ² In the treatment of macular hole, the therapeutic goal is to improve visual acuity and relieve metamorphopsia, the latter being a major source of dysfunction because it disturbs binocular vision. It has actually been suggested that removal or reduction of metamorphopsia correlates more closely with the likelihood of a perceived successful outcome than does the improvement in Snellen acuity. ³  

In addition to Amsler grid testing, at least five other psychophysical tests have been applied in the assessment of metamorphopsia in patients with macular hole. Nevertheless, objective methods of metamorphopsia assessment have rarely been included in interventional studies of macular hole. 

A classic qualitative metamorphopsia test used in the diagnosis of macular hole, the Watzke-Allen test, requires the patient to describe the appearance of a rectangular, illuminated field projected on the patient's fundus and centered on the macular hole during slit lamp biomicroscopy. ⁴ A similar approach is used in the Line Resolution Test, in which the subject has to decide for each pair of a series of line pairs, which line is distorted. ⁵  

Binocular perimetry was developed to assess photoreceptor displacement in patients with macular hole. ¹ The method maps metamorphopsia in subjects with a unilateral macular hole and a normal fellow eye by applying dichoptic stimuli to map corresponding retinal locations. 

M-CHARTS (Inami Co., Tokyo, Japan) can be been used to evaluate patients with macular hole ⁶ based on monocular testing using a hyperacuity (Vernier acuity) stimulus. 

Preview-PHP (Carl Zeiss Meditec, Jena, Germany) is another test based on a hyperacuity approach that was originally designed to assess metamorphopsia in AMD, but has been used also to detect metamorphopsia in eyes with macular hole. ⁷  

Assessment of metamorphopsia before and after surgical treatment for macular hole has only been made using a binocular perimetry technique reported by Jensen and Larsen and M-CHARTS. ^6,8 In contrast to the method used in the present study, these methods are not capable of measuring metamorphopsia as a function of visual field eccentricity. 

We have recently introduced a metamorphopsia test designed specifically for the quantification of visuospatial distortion in patients with unilateral macular hole. ⁹ The test measures visuospatial distortion as a function of eccentricity within the central 10° of the visual field, assuming an underlying circular pattern of photoreceptor displacement. In the prospective study presented herein, we assessed metamorphopsia in relation to visual field eccentricity before and after vitrectomy in 42 patients with idiopathic unilateral macular hole, to evaluate the degree of photoreceptor displacement after surgery and to determine the predictive value of preoperative metamorphopsia for predicting postoperative visual function. 

Methods

Subjects

Study participants were recruited from the Copenhagen Macular Hole (COMAH) study, a randomized, controlled clinical trial comparing different methods of surgical treatment for macular hole. Inclusion criteria were having a unilateral idiopathic macular hole Gass stage 2 or 3, a normal fellow eye, preserved binocular function, best corrected visual acuity (BCVA) in the macular hole eye better than or equal to 0.1 (34 letters on the Early Treatment of Diabetic Retinopathy Study [EDTRS] chart), duration of symptoms less than 12 months, and ability to complete 6 months of follow-up. Exclusion criteria were current or past macular hole in the fellow eye, failed surgical closure of the macular hole in the study eye, epiretinal fibrosis, prior intraocular surgery other than cataract surgery, disease other than macular hole affecting or potentially affecting retinal function, a history of glaucoma or glaucoma being diagnosed at a screening visit, amblyopia, nystagmus, and strabismus, refractive error greater than ±5 D, and anisometropia greater than 3 D. 

Baseline and 6-month follow-up examinations included a comprehensive ophthalmic examination including manual undilated refraction, assessment of BCVA at a 4-m distance, slit lamp biomicroscopy, mydriatic funduscopy, fundus photography, and optical coherence tomography (Stratus OCT3; Carl Zeiss Meditec, Dublin, CA). All patients who were phakic at inclusion underwent phacoemulsification with pseudophakic lens implantation 1 month before the baseline examination. The minimum inner diameter of the hole (minimum diameter) and the hole diameter at the level of the retinal pigment epithelium (maximum diameter) were measured with the built-in calipers of the system software. ¹⁰ In addition, patients completed a visual function questionnaire designed for the study. The questionnaire was presented to the patient and answered before the baseline examination. 

All patients underwent surgical treatment for macular hole and were studied before and after treatment. The standardized surgical procedure included pars plana vitrectomy, removal of the posterior hyaloid, fluid–gas exchange using C₃F₈ gas, and randomized assignment to plain vitrectomy or vitrectomy with internal limiting membrane (ILM) peeling, the latter subgroup again being randomized to vital dye staining with indocyanine green or trypan blue. Comparison of outcome for the different surgical subgroups is published in a separate article. ¹¹ Patients were asked to maintain face-down positioning during 10 hours per day for 5 days after surgery. 

The study enrolled 55 patients with a unilateral stage 2 (n = 19) or stage 3 (n = 36) macular hole. Preoperative interocular disparity findings in these 55 patients have been published. ⁹ Thirteen patients were excluded for various reasons: three did not achieve macular hole closure, one developed a macular hole in the fellow eye, six were unavailable for planned follow-up because of late enrollment, one withdrew from the study, and two did not undergo differential perimetry testing because of instrument failure. With the exclusion of the 13 patients, the present analysis includes 42 eyes in 42 patients. 

All participants gave written informed consent before inclusion. The study was approved by the medical ethics committee of Copenhagen County (KA04144) and registered with the National Institutes of Health as a clinical trial. The study was conducted according to the Declaration of Helsinki. 

Quantification of Metamorphopsia

The details of the retinal aniseikonia test have been described. ⁹ Test stimuli consist of two half-disks of different color presented dichoptically to the test participant wearing red and green filter glasses, one color for either eye. When seen by a healthy subject without aniseikonia, the two disks combine to form a single round disk divided vertically into two halves of equal size but different color. If the rim of the half-disks seen by the diseased eye is located at an eccentricity affected by metamorphopsia and micropsia produced by a centrosymmetric unilateral macular hole, the patient will see two unevenly sized half-disks. An operator then presents a series of combinations of unevenly and evenly sized half-disks and records the combinations that appear to the patient to form an intact and perfect disk, the two halves appearing to be of equal size. 

Micropsia is experienced by the patient because the image perceived by the eye having a macular hole is smaller than the image perceived by the normal fellow eye, the reference eye. This difference in perceived size is used in the test where the reference eccentricity is defined as the angular distance from the point of fixation to the rim of the reference stimulus presented to the normal eye. The test determines the eccentricity required for a test stimulus (presented to the diseased eye), to perceptually match the reference stimulus (presented to the normal eye). This difference in eccentricity is referred to as interocular disparity and will be used synonymously with metamorphopsia throughout this article, although, in principle, metamorphopsia can be both monocular and binocular. In the present context, we define the metamorphopsia function as interocular disparity in relation to the eccentricity of the rim of the reference stimulus. In patients with a unilateral macular hole concentric with the premorbid center of the fovea, interocular disparity is an angular measure of the radial displacement of photoreceptors away from the center of the foveola. 

The reference stimuli's diameter ranged from 2° to 10°, in increments of 2° (Fig. 1). This corresponds to radial eccentricities of 1° to 5°. Although smaller reference stimuli were possible indeed, smaller stimuli are often invisible to the eye with macular hole because their projection on the fundus fell entirely inside the physical defect in the retina. Test stimuli ranged from being identical with the reference stimulus to an additional width of up to 1.5°. One degree of visual angle is equal to 288 μm on the retina in the emmetropic eye. ¹² The total number of half-disk combinations was 20 pairs of red and green semicircular half disks, which were presented in random order at two sessions on the same day with a short break between the two test sessions. 

Figure 1.

 

Area of examination. Fundus photograph of macular hole with superimposed 2°, 4°, 6°, 8°, and 10° circles indicating the area of examination.

Data analysis was based on average responses during the two same-day sessions. The Mann-Whitney rank sum test was used to compare metamorphopsia parameters before and after treatment. One-way analysis of variance was used to describe the effect of eccentricity on interocular disparity. 

Results

The study population of patients with unilateral stage 2 or 3 macular hole tested immediately after and 6 months after surgery comprised 42 patients with a mean preoperative best corrected visual acuity in the macular hole eye of 51 ± 6 SD (range, 37–67 EDTRS letters; Table 1). The mean postoperative visual acuity was 68 ± 9 SD (range, 46–86 EDTRS letters). 

Table 1.

 

Characteristics of Patients with Unilateral Macular Hole and a Healthy Fellow Eye

Age, y
Range	54–78
Mean ± SD	67 ± 6
Sex
Male	6
Female	36
Spherical equivalent in study eye
Range	−4.6 to 1.8
Mean ± SD	−1.1 ± 1.3
Lens status
Phakic	0
Pseudophakic	42
Preoperative visual acuity study eye (ETDRS-letters)
Range	37–67
Mean ± SD	51 ± 6
Preoperative visual acuity control eye (ETDRS-letters)
Range	69–98
Mean ± SD	85 ± 5
Visual symptoms in daily activities (41 responders)
Image distortion	41/41
Micropsia	10/41
Macropsia	0/41
Surgical outcome
Macular hole closed after first operation	34
Macular hole closed after reoperation	8
Postoperative visual acuity study eye (ETDRS-letters)
Range	46–86
Mean ± SD	68 ± 9
Postoperative visual acuity control eye (ETDRS-letters)
Range	69–95
Mean ± SD	84 ± 5
Stage of macular hole
2	14
3	28
Minimum size of macular hole, μm
Range	199–735
Mean ± SD	438 ± 121
Maximum size of macular hole, μm
Range	623–1459
Mean ± SD	922 ± 216

  n = 42 eyes in 42 patients.

Preoperative interocular disparity was found to decrease with increasing eccentricity (P < 0.001), from a mean of 0.34° closest to the fovea, at 1° eccentricity, to a plateau of 0.2° at an eccentricity of 3° to 5° (Fig. 2). 

Figure 2.

 

Metamorphopsia before and after surgery. Mean interocular disparity in relation to reference eccentricity in 42 patients with uniocular stage 2 or 3 macular hole at baseline and 6 months after surgery. The interocular disparity level was significantly reduced at all eccentricities 6 months after surgery (P < 0.001). The largest changes were found in the smaller eccentricities (P < 0.001). Error bars, SD.

Six months after successful macular hole closure, the 42 patients demonstrated an interocular disparity that was independent of eccentricity (P = 0.962) and had a mean disparity below 0.1° (Fig. 2), which corresponds to a minor degree of nominal residual micropsia in the average patient. Compared to the preoperative baseline, interocular disparity at follow-up was reduced at all eccentricities (P < 0.001), the reduction being most prominent at smaller eccentricities (P < 0.001; Fig. 2). 

The maximum preoperative interocular disparity was higher than 0.125° in all patients and had a mean value of 0.35° (Fig. 3). After surgery, no interocular disparity was detected in 10 eyes, the mean value for the entire study population of 42 patients being 0.13° (Fig. 3). Surgery was associated with no change in maximum disparity in four patients, all of whom had a baseline maximum disparity of 0.25 or higher (Fig. 3). 

Figure 3.

 

Interocular disparity before and after surgical treatment of macular hole in 42 patients. Maximum disparity at baseline and at 6-month follow-up after successful treatment of idiopathic stage 2 or 3 macular hole in 42 patients. In 10 patients, no visuospatial distortion was detectable at the 6-month follow-up. Four patients did not show any change in maximum distortion value.

Disparity was decreased in at least one or more eccentricities in all patients. Nine patients even demonstrated negative disparities corresponding to macropsia (range, −0.0625 to −0.25°) at some eccentricities, but no patient had consistent macropsia at all eccentricities. 

Examination of postoperative retinal ultrastructure with optical coherence tomography demonstrated discontinuities in the photoreceptor layer in 13 of 42 eyes. No correlation was found between this feature and interocular disparity at 1° eccentricity (χ² = 1952 with 1 df; P = 0162) or visual acuity (mean 64 vs. 69 EDTRS letters; P = 0.08). 

A post hoc analysis of baseline interocular disparity at 1° eccentricity demonstrated that when patients were stratified by disparity, <0.35° versus >0.35°, the former achieved better final visual acuity than the latter (mean, 73 EDTRS letters vs. 64 EDTRS letters, P < 0.001; Fig. 4). This finding was supported by correlation analysis of visual acuity at 6 months and baseline interocular disparity at 1° eccentricity (n = 42, r = −0.39, P = 0.01). 

Figure 4.

 

Prognostic value of preoperative disparity. Stratification of patients according to interocular disparity. At 1° eccentricity, patients with interocular disparity < 0.35° showed 9 more EDTRS letters improvement in final visual acuity (95% confidence interval, 14–4 EDTRS letters) than did patients with disparities > 0.35°.

Discussion

The present study is the first conducted to evaluate interocular photoreceptor displacement and repositioning after macular hole surgery as a function of retinal location and visual field eccentricity. After surgery, a significant reduction in metamorphopsia was found in the population as a whole, and maximum interocular disparity in perceived stimulus size was reduced in 38 of 42 patients. Lesser degrees of preoperative interocular disparity near the margin of the macular hole were associated with a better visual outcome. In relation to retinal location, this means that the largest preoperative displacement of photoreceptors away from the center of the visual field was associated with the least successful repositioning of photoreceptors, despite biomicroscopic and tomographic hole closure. 

Visuospatial distortion assessment appears to reflect aspects of vision that are of functional importance to the patient. Not only does metamorphopsia degrade vision when it affects an only seeing eye, it can also degrade binocular function in patients with a normal fellow eye. 

To fully understand macular hole disease and the effect of interventions, assessment of photoreceptor structure and function should be made before and after surgery. In the present study, in 13 eyes OCT demonstrated a persistent foveolar gap in the photoreceptor layer after surgery despite, anatomic hole closure. Our data did not permit evaluation of whether this is caused by incomplete photoreceptor repositioning or loss of photoreceptors. We did not, however, find any effect on final visual acuity of the photoreceptor layer discontinuity, unlike a previous surgery study in which poor final visual acuity was related to discontinuity of the photoreceptor band on OCT after surgery, ¹³ but in agreement with a study of 14 eyes in which macular holes closed spontaneously. ¹⁴ These discrepancies may be caused by the limited resolution of the OCT procedure used in this study. Histopathology has shown that photoreceptor atrophy in eyes with macular hole can vary markedly in severity and in extent, ranging from 200 to 750 μm from the edge of the hole margin. ¹⁵ Higher resolution OCT has indeed supported these findings ^16–18 and has shown signs of other postoperative conditions such as disruption of multiple retinal layers, cystoid foveal spaces, and persistent foveal detachment. ¹⁸  

Idiopathic macular hole has long been recognized as a condition associated with tangential photoreceptor displacement. ^1,8,19,20 Cerebral cortical plasticity is often suggested as a mechanism that could lead to a compensatory remodeling of perceptual projection of receptor units in visual space, but the strong association between interocular disparity in patients with a unilateral macular hole and subsequent reduction or elimination of disparity after macular hole closure does not support any role for cortical plasticity in compensating for the distortion induced by the deformation of the retina. Indeed, we previously found that the angular maximum interocular disparity was generally within the limits predicted by the smallest hole diameter expressed in degrees of visual angle. ⁹  

In the present study, we found a roughly biphasic shape of the disparity versus eccentricity function (Fig. 2), the trend being nearly flat from 3° to 5°. This suggests that two types of photoreceptor displacement act in concert in eyes with a macular hole: tangential displacement and inner margin eversion (Fig. 5). Thus, eversion of photoreceptors along the free margin of the hole could be responsible for the steep part of the curve closest to the center of the fovea, whereas tangential photoreceptor displacement could be responsible for the flatter part of the curve corresponding to higher distances from the fovea. This hypothesis is supported by the typical finding on OCT images of a central full-thickness defect in the neuroretina surrounded by a thickened retina and an accumulation of subretinal fluid that often covers a much larger area than the hole itself. ²¹ Near the margin of the hole, a portion of the detached retina often appears to have been partially everted, in the shape of a bascule bridge pivoted at the photoreceptor-RPE junction at the subretinal edge of the hole. This formation is difficult to validate by inspection of the OCT scan, because the thickening of the retina disturbs the layered architecture of the retina and induces scatter that attenuates the image of the outer aspect of the retina and because rotation of the retina must be assumed to alter its reflectivity as seen from the direction of the pupil. Nevertheless, histopathologic studies of idiopathic macular holes show that even after 3 years, intact photoreceptors can be found on the elevated rim of the hole. ²² Furthermore, ultrahigh-resolution OCT images of idiopathic macular holes suggest that an intact band of photoreceptor outer segments is found from the subretinal rim to the inner edge of the hole. ¹⁶  

Figure 5.

 

Proposed mechanism of photoreceptor displacement and induction of metamorphopsia in eyes with macular hole by a combination of eversion and tangential centripetal movement. Arrows: direction of displacement. The thickness of the arrows indicates the magnitude of displacement. White circles indicate that the detached lip of the macular hole is everted by rotation about a pivotal junction between the photoreceptors and the RPE at the subretinal edge of the hole.

Our data suggest that eversion of the outer retina is an essential mechanism of photoreceptor displacement and induction of metamorphopsia (Fig. 5). In addition, the finding of residual metamorphopsia that is independent of eccentricity after biomicroscopically successful surgical repair of a macular hole suggests that photoreceptor repositioning is incomplete (Fig. 6). According to this theory, closure of the macular hole by elimination of eversion may be complete and sufficient to close the hole, yet residual tangential displacement may be found even after the inner layers of the hole have closed. It could be argued that the residual metamorphopsia detected after surgery with our test is the result of random variation around the mean. However, 11 healthy subjects expressed a median interocular disparity of 0.0° for all but one stimulus size in a previously reported study. ⁹  

Figure 6.

 

Proposed anatomic structure of the retina after biomicroscopic closure of the hole with a persistent discontinuity of the photoreceptor outer segment layer (gray box). Arrows indicate that despite elimination of eversion and reattachment of the retina, residual tangential displacement was responsible for a central defect in the photoreceptor matrix that may help explain why residual metamorphopsia that was independent of eccentricity was found after successful surgery in 32 of 42 patients.

All patients in our study showed evidence of some degree of photoreceptor displacement in the eye with the macular hole, and patients having less than 0.35° of interocular disparity at 1° eccentricity at baseline showed higher postoperative visual acuity. This observation corroborates those in previous studies showing that a small macular hole diameter is associated with a better functional outcome. ^23,24 Although macular hole and central scotoma but no evidence of photoreceptor displacement have been described in 25% of the cases in a previous study, ⁸ no such patient was found in our study. Absence of detectable disparity and, hence, photoreceptor displacement, suggests the presence of full-thickness loss of a portion of the foveal retina or loss of photoreceptor function and viability near the rim of the hole. The complete absence of eyes without evidence of photoreceptor displacement in our study indicates to us that the latter mechanism is the most likely. In the present study, we found consistent visual improvement after surgery, supporting that macular hole surgery is an attractive therapeutic option independent of preoperative visual acuity and duration of symptoms, within the range represented here and in studies with similar findings. ²⁵  

In conclusion, we have found that metamorphopsia related to photoreceptor displacement in eyes with a macular hole can be assessed objectively by using a simple test object designed specifically for this condition and expressed in degrees of interocular disparity before and after surgical treatment. Furthermore, the study showed that preoperative interocular disparity near the center of the visual field predicts final best corrected visual acuity. In our study population, macular hole surgery was followed not only by improved visual acuity but also by a considerable reduction in disparity that is likely to be of benefit for binocular visual function, visual comfort, and visual stamina when reading or performing near-vision tasks, especially those that require stereo acuity. 

Footnotes

 Supported by the Danish Eye Health Society (Værn om Synet), the Danish Medical Research Council, the Velux Foundation, and Grant 8-2002-130 from the Juvenile Diabetes Research Foundation.

Footnotes

 Disclosure: K. Krøyer, None; U. Christensen, None; M. la Cour, None; M. Larsen, None

Footnotes

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