title: Tests of Macular and Perimacular Vision (MAVIS)
Creators: name: Alrumizan, Meshary Rumizan M
Publisher: name: University of Liverpool Repository
Year: 2023

description: Purpose:
Early treatment gives better outcomes in people with several common macular diseases but detecting them in a timely manner is challenging. Currently established tests of visual function often miss early macular disease. The handheld radial shape discrimination (RSD, hRSD) test has shown promise for the earlier detection of macular pathology. However, the hRSD test is sensitive only for the central 1° of visual function. Contour integration macular perimetry (CIMP) is believed to measure function outside the central 3° of visual function (perimacular area). Whether CIMP is able to detect the subtle impairment of visual function caused by retinal pathology remains to be investigated. I investigated the performance of both the hRSD and CIMP tests and how these two tests relate to each other and to conventional static visual acuity (VA) in healthy participants and patients with diabetic maculopathy and age-related macular degeneration (AMD).

Methods:
Three groups of participants were studied in a cross-sectional design. Healthy controls were recruited through local announcements. Patients with early diabetic maculopathy (EDM) were recruited from people who attended for routine diabetic retinopathy screening in Liverpool and were graded screen +ve with diabetic maculopathy (English National Diabetic Eye Screening criterion M1). Patients with macular neovascularisation (MNV) secondary to AMD were recruited from people referred into the Liverpool macular degeneration service with suspected MNV and confirmed by a panel of clinical experts. All eyes of the MNV group were classified against Age-related Eye Disease Study and Consensus on Neovascular Age-related Macular Degeneration Nomenclature Study Group (CONAN) criteria.
Inclusion criteria for healthy participants: minimum age 18 years, good general health with good vision (self-reported), able and willing to provide informed written consent.
Exclusion criteria: Previous or current diagnosis of any ocular pathology, other concurrent health problems such as diabetes or hypertension, VA worse that 6/12 (logMAR +0.30) in either eye.
Inclusion criteria for the patients were: minimum age 18 years; able to provide informed written consent, with the diagnosis of diabetic maculopathy or MNV. Exclusion criteria were: concurrent macular pathologies in addition to the target condition (eg. intermediate to severe geographic atrophy, epiretinal membrane), intraocular surgery in the previous 6 months, inability to perform tests (eg. severe arthritis, severe tremor).
Tests of visual function were recorded using log of the minimum angle of resolution (logMAR). RSD was recorded using an iPad and, for healthy participants only, an iPhone; the hRSD protocol comprised 4 alternate forced choice stimuli of 1° radius. CIMP stimuli consisted of four circular contour segments on an iPad, each a 30° circular arc, evenly placed along the centre of either an inner (iCIMP) ring (~4° radius) or outer (oCIMP) ring (~8° radius). Distance VA was recorded using Early Treatment of Diabetic Retinopathy Study (ETDRS) charts. Tests were repeated twice for each eye with the other eye patched; if there was a difference of ≥0.30 logMAR between the first two tests, a third test was performed. A useability questionnaire was developed to assess ease of use.

Results:
In 85 healthy controls (mean ±SD age 32.27 ±10.21 years, range 18-65; female/male, 35/50) VA for distance and near were strongly correlated between the right and left eyes (r=0.70, p&lt; 0.001; r=0.61, p&lt;0.001 respectively). The mean (±SD) for the four tests of vision were: hRSD -0.78 ±0.11, iCIMP -0.80 ±0.10, oCIMP -0.81 ±0.10, distance VA -0.07± 0.10. The slope of the least square regression line for distance VA was -0.0008 compared to hRSD -0.0007. Both these slopes showed no association with age.
In 96 patients (after data exclusions) with EDM (62.26 ±13.11 years, range 28-92; female/male, 35/65) the digital hyperacuity was significantly reduced compared to healthy controls: hRSD -0.47 ±0.22, iCIMP -0.49 ±0.19 and oCIMP -0.61 ±0.16 (all p&lt;0.0001). Hyperacuity. DVA was also reduced in EDM (0.16 ±0.23) however hyperacuity was affected more. No correlation was found between the hyperacuity performance and the central subfield thickness on optical coherence tomography (OCT).
In 46 patients (after exclusions) with newly diagnosed MNV (74.72 ±9.40 years, range 59- 86; female/male, 32/18) the digital hyperacuity was substantially reduced: hRSD -0.14 ±0.38, iCIMP -0.05 ±0.51, oCIMP -0.18 ±0.48 (all p&lt;0.001). The effect on hyperacuity was greater than for distance VA (0.55 ±0.32, p&lt;0.001). A subgroup analysis of all eyes after classification into AMD groups (n=94) showed progressive worsening of hyperacuity with increasing disease severity (ANOVA hRSD F3,90=10.17, iCIMP: F3,90=7.76, oCIMP: F3,90=3.55; all p&lt;0.05). In a combined AREDS (early AMD) group the iCIMP showed a sensitivity and specificity for distinguishing from MNV of 75.5% (both) (AUROC 0.73, p&lt;0.001).
The digital hyperacuity tests were easy for all groups to perform. hRSD was time consuming especially for the patient groups.

Discussion:
I presented normative data for hRSD, adding to and confirming existing data, and new data for CIMP. In MAVIS there was no significant difference with increasing age. Taken together with the published evidence these findings suggest that age has only a small impact on digital hyperacuity, unlike its effect on distance and near VA.
In both groups of early macular disease there was evidence of substantial loss of hyperacuity function in central, peri- and paramacular zones. Perimacular hyperacuity (iCIMP) appeared to be more sensitive than paramacular (oCIMP). In MNV this effect on the iCIMP was greatest at 0.75 logMAR, roughly equivalent to 7.5 lines worse on an ETDRS chart.
Subgroup analyses showed a relationship between loss of hyperacuity and progression of disease in the MNV group, but not in the EDM group. There was evidence of a possible target group (60%) in patients with MNV in one eye and early AMD in the fellow eye with loss of hyperacuity but minimal loss of distance VA.
In the EDM group the results support the expert consensus that M1 is early in the natural history of diabetic maculopathy when sight is not yet affected. It would be interesting to investigate the use of digital hyperacuity tests in people with later disease.

Conclusions:
There was a clear worsening of hyperacuity as measured by digital tests in patients with early macular disease compared to healthy controls. Notably, hyperacuity was reduced in all three tests in the EDM group, especially hRSD and iCIMP suggesting some increased sensitivity of digital hyperacuity tests to EDM. iCIMP may be useful in detecting MNV in fellow eyes with early AMD, targeted on a group of patients with preserved distance VA. The iCIMP may be more sensitive and quicker compared to other tests of visual function and add new information in the clinical care of macular disease in a range of clinical settings.