The natural history of lamellar macular holes: a

The natural history of lamellar macular holes: a spectral domain optical coherence tomography study Ferdinando Bottoni, Antonio Peroglio Deiro, Andrea Giani, Claudia Orini, Mario Cigada & Giovanni Staurenghi Graefe's Archive for Clinical and Experimental Ophthalmology Incorporating German Journal of Ophthalmology ISSN 0721-832X Volume 251 Number 2 Graefes Arch Clin Exp Ophthalmol (2013) 251:467-475 DOI 10.1007/s00417-012-2044-2

1 23

Your article is protected by copyright and all rights are held exclusively by SpringerVerlag. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to self-archive your work, please use the accepted author’s version for posting to your own website or your institution’s repository. You may further deposit the accepted author’s version on a funder’s repository at a funder’s request, provided it is not made publicly available until 12 months after publication.

1 23

Author's personal copy Graefes Arch Clin Exp Ophthalmol (2013) 251:467–475 DOI 10.1007/s00417-012-2044-2

RETINAL DISORDERS

The natural history of lamellar macular holes: a spectral domain optical coherence tomography study Ferdinando Bottoni & Antonio Peroglio Deiro & Andrea Giani & Claudia Orini & Mario Cigada & Giovanni Staurenghi

Received: 1 March 2012 / Revised: 10 April 2012 / Accepted: 16 April 2012 / Published online: 9 May 2012 # Springer-Verlag 2012

Abstract Background To study the evolution of lamellar macular holes (LMHs) using spectral domain-optical coherence tomography (SD-OCT). Methods Thirty-four consecutive patients diagnosed with a LMH were followed prospectively at Sacco University Hospital from October 2008 to January 2011. Inclusion criteria were a foveal defect on SD-OCT with residual foveal tissue above the retinal pigment epithelium and corresponding hyperautofluorescence on fundus autofluorescence imaging. Epiretinal membranes (ERMs) were categorized by SDOCT at baseline as two different types: normal and thicker than normal. Best corrected visual acuity (BCVA) and SDOCT findings were collected and compared at baseline and every 6 months thereafter. Active eye tracking technology ensured that the same scanning location was identified on follow-up visits. Main outcome measures were visual acuity changes (Early Treatment Diabetic Retinopathy charts) and progression of the lamellar macular defect. The influence of ERM type on disease progression was also evaluated. Results The patients included 15 males and 19 females with a mean age of 73 years and mean refraction of −0.25 Presented in part at the Association for Research in Vision and Ophthalmology Annual Meeting, Fort Lauderdale, FL, USA, May 2010 and at the 11th Euretina Congress, London, UK, May 2011 This study had no financial support. The authors have full control of all primary data and they agree to allow Graefes Archive for Clinical and Experimental Ophthalmology to review their data if requested. F. Bottoni (*) : A. P. Deiro : A. Giani : C. Orini : M. Cigada : G. Staurenghi Eye Clinic, Department of Clinical Science “Luigi Sacco”, Sacco Hospital, University of Milan, Via Andrea Verga 8, 20144 Milano, Italy e-mail: [email protected]

diopters. The mean follow-up period was 18 months (range 6 to 24 months). BCVA at baseline (±standard deviation) was 63±6 letters and did not change significantly during the follow-up period (P00.256). Foveal thickness at baseline, 180±29 μm, was also stable (P00.592). All eyes had an ERM at baseline. Both thicker and normal ERMs showed similar functional and morphological evolution during follow-up with no significant changes. Two LMHs (5.8 %) developed a full thickness macular hole after 6 and 15 months follow-up respectively. Conclusions Lamellar macular holes seem to be a stable macular condition. Vitrectomy should be considered only in the presence of progressive thinning of foveal thickness and/or decrease of visual acuity during the follow-up of the disease. Keywords Lamellar macular hole . Spectral domain optical coherence tomography . Natural history

Introduction Lamellar macular holes (LMHs) are distinct clinical entities, and as originally described by Gass using biomicroscopy [1], they have a reddish oval appearance. The description and pathogenesis of LMHs have been better understood with the advent of optical coherence tomography (OCT)[2–9] and fundus autofluorescence (FAF) imaging [10]. With time domain OCT (TD-OCT), LMHs were described as partial thickness defects of the macula with an irregular foveal contour and a schisis between inner and outer retinal layers, but without any defect of the photoreceptor layer [2–5, 7]. By definition, LMHs are macular lesions with loss of foveal tissue [7, 9] as opposed to pseudo-macular holes. Despite specific criteria, OCT imaging cannot determine with certainty whether or not loss of tissue has occurred. FAF imaging is of great help in this

Author's personal copy 468

regard. Any foveal defect, including LMHs, that spare the photoreceptors, may increase the degree of foveal autofluorescence (AF) by decreasing the amount of masking macular pigment. Thus, the presence of foveal AF is always consistent with a diagnosis of LMH [10]. LMHs might be the result of abortive development of full thickness macular holes [2–4]. Alternatively, they may represent a complication of chronic cystoid macular edema [1], or they may be related to the contraction of the existing perifoveal epiretinal membrane (ERM)-internal limiting membrane (ILM) complex [9, 11, 12]. LMH patients commonly have relatively good visual acuity (VA), usually 20/ 40 or better. OCT studies related to LMH investigation are mainly concentrated on the differential diagnosis [7, 9] and on the results after surgical intervention [12–16]. There is only one large series recently published on the natural evolution of LMHs [17]. However in that study, OCT examinations were performed by TD-OCT that is inherently limited to 10 μm axial resolution, and the low acquisition speed limited the detailed analysis of pathologic changes. By contrast, spectral domain OCT (SD-OCT), with 5- to 7-μm axial resolution, allows clear detection of the inner segment/outer segment (IS/OS) line and the external limiting membrane (ELM), that is the junction between the inner segments and Muller cells. The purpose of our investigation was to assess by SD-OCT the natural course of LMHs in a series of consecutive patients during a mean follow-up of 18 months.

Material and methods We studied 34 eyes in 34 consecutive patients diagnosed with a LMH and followed prospectively at Sacco University Hospital from October 2008 to January 2011. All examinations and investigations adhered to the tenets of the Declaration of Helsinki. This study was approved by the Institutional Review Board Committee of Milan University Medical School at Sacco Hospital. At baseline, each patient underwent a complete ophthalmologic examination, including intraocular pressure measurement, lens clarity evaluation, refraction, and biomicroscopic examination of the fovea and vitreous. The best corrected visual acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) charts. A combined confocal scanning laser ophthalmoscope and SD-OCT instrument (Spectralis HRA + OCT, Heidelberg Engineering GmbH, Heidelberg, Germany) was used for macular examination. Diagnosis of LMH was established in the presence of a foveal defect on SD-OCT and corresponding hyperautofluorescence on FAF imaging [10]. The OCT definition of “foveal defect” included 4 criteria: (1) an irregular foveal contour, (2) a break in the inner fovea, (3) a dehiscence of the inner foveal

Graefes Arch Clin Exp Ophthalmol (2013) 251:467–475

retina from the outer retina, and (4) an absence of a full thickness foveal defect with intact foveal photoreceptors [9]. In case of uncertainty, hyperautofluorescence on FAF imaging was considered decisive (Fig. 1a and b). The size of each LMH was calculated using the largest diameter recorded in FAF images. During the baseline visit, two different types of ERMs were identified based on OCT images. Normal ERMs (Fig. 1c) appeared as a thin highly-reflective line immediately anterior to and separate from the retinal nerve fiber layer (RNFL). Thicker ERMs (Fig. 1d) appeared as moderately-reflective material filling the space between the inner border of the ERM and the RNFL [9]. A complete posterior vitreous detachment (PVD) was diagnosed using either the SD-OCT and biomicroscopy. On SD-OCT, the diagnosis was established when the hyaloid condensation was visible clearly on the scans. By biomicroscopy, a complete PVD was diagnosed when the Weiss ring was detected. Patients with current eye disease other than LMH, opaque media, or refractive error exceeding ± 6 diopters (D) were excluded. For patients who met the inclusion criteria, a detailed explanation of the study was provided at the initial visit, and informed consent was obtained. Follow-up visits including measurements of BCVA and SD-OCT evaluations were scheduled every six months. Confocal scanning laser ophthalmoscopy and SD-OCT by the Spectralis HRA + OCT provides up to 40,000 A-scans/sec. The axial digital resolution is 3.9 μm in tissue and the transversal digital resolution is up to 15 μm (high-resolution mode) with the superluminescence diode at 870 nm central wavelength. The instrument combines SD-OCT technology with a confocal scanning laser ophthalmoscope that provides a reference fundus image based on infrared and blue reflectance and blue laser autofluorescence. Using active eye tracking technology, the system automatically follows eye movements and locks each OCT B-scan to the fundus image, ensuring exact registration. The “AutoRescan” function identifies previous scan locations and automatically guides the OCT instrument to scan the same location again for follow-up visits. For the purpose of this study, the first complete volume scan acquired at baseline was set as a reference scan. Active real-time eye tracking and high scanning speed reduce movement artifacts. For OCT scanning, the software provides an “Automatic RealTime” (ART) function to reduce noise and increase image quality. With ART activated, multiple frames (B-scans) of the same scanning location are performed during the scanning process, and images are averaged for noise reduction. In this study, 20 frames were acquired and averaged for each B-scan location. For LMH analysis, raster scans of 30°×15° (8.7× 4.3 mm, including the optic disc) and consisting of 19 to 25 line scans were performed. The spacing between the B-scans ranged from 119 to 271 μm. An internal fixation light was used to center the scanning area on the fovea.

Author's personal copy Graefes Arch Clin Exp Ophthalmol (2013) 251:467–475

469

Fig. 1 Baseline images of a foveal lesion. a Fundus autofluorescence image showed a foveal lesion of 330 μm. b The corresponding spectral domain optical coherence tomography (SD-OCT) revealed only an irregular foveal contour with intact foveal photoreceptors. Foveal thickness (arrow) was measured from the retinal pigment epithelium

to the internal limiting membrane. c SD-OCT of a normal epiretinal membrane (ERM, within circle). d SD-OCT of a thicker ERM with moderately-reflective material filling the space between the inner border of the ERM and the retinal nerve fiber layer (within circles)

Main outcome measures were VA changes and progression of the lamellar macular defect. The latter was evaluated by measuring with software calipers the distance between the ILM interface and the retinal pigment epithelium at the thinnest point in the fovea (Fig. 1b). Secondary outcomes were the influence of ERM type on disease progression and the correlation between retinal thickness and BCVA at baseline. For all computations, commercially available software was used (R; R Foundation for Statistical Computing, Vienna, Austria). Changes of VA and OCT findings over time as well as the influence of ERM type on disease progression were evaluated using ANOVA for repeated measures. P