REVIEW URRENT C OPINION
Introduction to microperimetry and its use in analysis of geographic atrophy in age-related macular degeneration Mostafa Hanout, Nicholas Horan, and Diana V. Do
Purpose of review This article discusses recent advances in the fundus-guided perimetry (microperimetry) and its utilization in evaluation and monitoring of patients with geographic atrophy. Recent findings Although best-corrected visual acuity has been gold standard in clinical practice for decades, it does not provide an entire assessment of visual function that determines daily activity and quality of life of a patient. Furthermore, psychophysical tests, including low-luminance visual acuity, reading speed, and contrast sensitivity, cannot be used to quantify retinal sensitivity or detect pattern of retinal dysfunction. Microperimetry provides a true evaluation of visual function by offering fundus-controlled testing through eye-tracking technology that allows for structural and functional correlation and test–retest reliability for the same test point. Furthermore, it enables precise assessment of location and stability of fixation. Recent research has shown microperimetry to be more representative of the macular function in macular diseases. Summary Microperimetry is currently the clinical investigation of choice to assess residual visual functions and functional vision in macular degenerative diseases, especially geographic atrophy. There is an increasing popularity to employ microperimetry in clinical trials investigating new treatments for geographic atrophy, as well as other macular degenerative diseases, as a reliable functional outcome measure. Keywords fixation, geographic atrophy, microperimetry, preferred retinal locus, retinal sensitivity
INTRODUCTION The advances in retinal imaging technologies have revolutionized contemporary diagnostic in ophthalmology and enabled early detection along with documentation of treatment results of retinal diseases. Precise clinical evaluation of retinal, especially macular involving, diseases necessitates correlating both the morphological and the functional aspects. The latter is more self-appreciated by patients, as major visual tasks determining the quality of life of patient grossly depend on it [1]. For decades, best-corrected visual acuity has been the gold standard in clinical practice; however, it does not represent an entire assessment of macular function. There are several puzzling presentations by patients whose visual function is inconsistent with visual acuity such as patients with paracentral macular lesions sparing the foveal center. Several psychophysical tests have been utilized, in addition to visual acuity, to evaluate macular function such as Amsler grid, contrast sensitivity, reading speed, and
low-luminance visual acuity among others. However, none of these testing parameters has proved ability to quantify retinal sensitivity or detect pattern of retinal dysfunction [2–4]. For many years, conventional static perimetry has been established as an essential clinical tool for quantification of visual field and retinal threshold especially in glaucoma and neuro-ophthalmological disorders. Nonetheless, it is often inadequate for accurate evaluation of macular function, especially with troublesome eccentric or unsteady fixation, or both [1,5,6].
Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA Correspondence to Diana V. Do, MD, Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, 985540 Nebraska Medical Center, Omaha, NE 68198-5540, USA. Tel: +1 402 559 4276; fax: +1 402 559 5514; e-mail: [email protected] Curr Opin Ophthalmol 2015, 26:149–156 DOI:10.1097/ICU.0000000000000153
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Retinal, vitreous and macular disorders
KEY POINTS Best-corrected visual acuity, psychophysical tests, and conventional perimetry, albeit useful, do not fulfill the desired comprehensive assessment of macular function in macular degenerative diseases. Residual visual function has more impact on the patient daily activity and quality of life. Microperimetry is currently the clinical investigation of choice to assess residual visual functions and functional vision in macular degenerative diseases, especially geographic atrophy. Microperimetry offers fundus-controlled testing of retinal sensitivity through eye-tracking technology that allows for structural and functional correlation and test–retest reliability for the same test point. Furthermore, it enables precise assessment of location and stability of fixation. Recent trends may call for incorporating microperimetry as a standard functional outcome measure in clinical trials of geographic atrophy.
More recently, microperimetry has effectively provided fundus-correlated functional testing, test–retest reliability for the same test point, precise assessment of the location and stability of fixation, and compensation for ocular movements. By incorporating these features, microperimetry has become the clinical investigation of choice to assess residual visual functions and functional vision in macular diseases [7,8]. This article covers basic concepts and recent advances in microperimetry, common marketavailable microperimeters, and the steadily growing role of microperimetry in clinical evaluation and monitoring of macular diseases, particularly, geographic atrophy. Latest research observations reported during the review period are also summarized.
fundus observation during examination [9]. The main challenge was that the bright light necessary for adequate retinal illumination will interfere with functional testing. With the advent of scanning laser ophthalmoscope (SLO), the infrared light source permitted simultaneous observation of the fundus during examination and led to introduction of the first microperimeter (SLO 101, Rodenstock, Ottobrunn, Germany) in the year 1982 [9,10]. Shortcomings of this device included semiautomated stimulus presentation and lack of eye tracker to compensate for ocular movements; the device is no longer available in the market. These limitations have been overcome by Nidek MP-1 (Nidek Technologies, Padova, Italy) that was introduced to the market in 2003 as the first fundus perimeter with eye tracker that compensates for eye movements based on an initial frame. With these new features in Nidek MP-1, exact correlation between retinal disorder and functional defects was rendered possible even in eyes with poor or unstable fixation [11,12 ,13,14]. Thereafter, in 2006, a more recent Spectral OCT/SLO microperimeter was introduced to the market by OPKO/OTI (OPKO Instrumentation, Miami, Florida, USA) that incorporated spectral optical coherence tomography (OCT) with microperimetry, offering an additional advantage of correlating retinal dysfunction with the corresponding ultrastructural finding as shown by OCT. The technology was later transferred to Optos Inc., and the device was named Optos OCT/SLO (Optos, Dunfermline, Scotland, UK). Optos OCT/ SLO is the only US Food and Drug Administration-approved microperimeter; it received 510(k) clearance in 2013 [3,15–18]. Macular Integrity Assessment (MAIA; CenterVue, Padova, Italy) was the latest instrument to reach the market in 2009, garnished with high-frequency eye tracker and a line confocal SLO [6,7]. Table 1 summarizes key differences between the three commercially available microperimeters. &
EVOLUTION OF MICROPERIMETRY According to many experts in the field, ‘microperimetry’ is not the most accurate naming for this ocular imaging technology, given the currently used examination parameters of stimulus size ranging from Goldman I to V, and examination field of up to 158–208 from the foveal center. Rather, ‘fundus-correlated perimetry’ or ‘fundus-guided perimetry’ are considered more accurate names. For sake of simplicity, we used the term ‘microperimetry’ throughout the article [5,6]. The need to achieve correlation between clinically apparent retinal disorder and functional testing urged the demand to design a perimetry device that enables 150
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CLINICAL APPLICATIONS OF MICROPERIMETRY Indeed, microperimetry surpasses conventional perimetry in several aspects in evaluation of retinal sensitivity in macular diseases [19]. One fundamental advantage of microperimetry is the real-time tracking of the fundus throughout perimetric testing. This allows perimetric examination of patients with eccentric or unstable fixation. The ability of registration of macular sensitivity results on digital fundus photograph allows for functional and structural correlation [6]. Furthermore, in conventional perimetry, the stimulus is projected on a screen in front Volume 26 Number 3 May 2015
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Introduction to microperimetry and its role in analysis of geographic atrophy Hanout et al. Table 1. Summary of commercially available microperimeters
Manufacturer
Nidek MP-1
Optos OCT/SLO
MAIA
Nidek Technologies, Padova, Italy
Optos, Dunfermline, Scotland, UK
CenterVue, Padova, Italy
Year of arrival to the market
2003
2006
2009
Features of incorporated fundus imaging
Infrared and digital color
SLO black and white
SLO black and white
458
29.78
368
Fixation assessment
Eye-tracking technology
SLO
High-frequency eye tracker
Background luminance
1.27 cd/m2
10 cd/m2
Microperimetric examination parameters Size of the of the microperimetry testing field
2
1.27 cd/m2 2
Highest stimulus intensity
128 cd/m
125 cd/m
318 cd/m2
Dynamic range of stimulus attenuation
0–20 dB
0–20 dB
0–36 dB
Coregistration of retinal sensitivity map on the fundus image
Automatic or Manual Options
Automatic with simultaneous SLO and OCT
Automatic coregistration
Advantages and unique features
Continuous fundus autofocus
Combined OCT for structural and functional correlation
High-resolution fundus imaging 1024 1024
Automatic retest
Available
Available
Available
Biofeedback training
Biofeedback training
MAIA, Macular Integrity Assessment; OCT, optical coherence tomography; SLO, scanning laser ophthalmoscope.
of the patient’s eye, whereas in microperimetry, the stimulus is directly projected on the predefined retinal points helped with the eye-tracking technology. This is another key advantage that allows for accurate test–retest of the same point in microperimetry with a shift range of about 0.538. On the other hand, sensitivity of a given point in conventional perimetry represents, in fact, the average of an area of about 58 [8]. The development of multiple commercially available microperimeters, such as Nidek MP-1, Optos OCT/SLO, and MAIA, has led to widespread use of microperimetry and allowed thorough evaluation of the device in clinical studies. Since late 80th of the last Century, microperimetry has been investigated in enormous number of clinical studies. It was shown to play a great role in diagnosis and follow-up of myriad of retinal and macular disorders including age-related macular degeneration (AMD) [20,21], geographic atrophy [22,23,24 ,25,26], choroidal neovascularization [27], diabetic retinopathy [15–17,28], uveitic macular edema [29–31], central serous chorioretinopathy [32], and macular dystrophies such as Stargardt’s disease [33] and North Carolina dystrophy [34]. Moreover, it has been instrumental in evaluating treatment results of several pharmacological therapies, as well as laser and surgical procedures. Examples include intravitreal antivascular endothelial growth factor for treating neovascular AMD [35], retinal laser photocoagulation for diabetic macular edema [36], and pars plana vitrectomy for macular holes [37,38]. There is no &
doubt that this innovative imaging modality, microperimetry, has significantly increased our knowledge and understanding of many macular disorders. For instance, microperimetry revealed the presence of dense scotomas over macular holes [37] and over macular areas where there is loss of integrity in the inner segment/outer segment layer [15]. Similarly, detecting the shift of preferred retinal locus (PRL) from the foveal center to the intact retina superior to central scotomas in macular holes or paracentral scotomas in number of other macular dystrophies would have not been possible without microperimetry [5]. In general, clinicians and researchers should be familiar with the features of different commercially available microperimeters so that they can select the version that services their purposes. For instance, Optos OCT/SLO may be the best choice for retina specialists practicing medical and surgical retina as it combines OCT with microperimetry (Fig. 1). On the other hand, those who practice low vision rehabilitation for patients with macular degenerative diseases such as geographic atrophy will benefit from the biofeedback training module in Nidek MP-1 and MAIA.
ROLE OF MICROPERIMETRY IN ANALYSIS OF GEOGRAPHIC ATROPHY The term ‘geographic atrophy’ was devised by the pioneer J. Donald M. Gass in 70th of the last century who first used it to describe discrete single or
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FIGURE 1. Combination of functional assessment using microperimetry and morphological assessment using OCT are combined in the Optos OCT/SLO Microperimeter (Optos, Dunfermline, Scotland, UK). The retinal sensitivity grid is imposed on the fundus image. The horizontal (blue line) and the vertical (green line) OCT scans crosses at one point that shows an absolute scotoma (0 dB). This enables precise structural and functional evaluation of the exact location in the fundus. In the bottom right corner of the image, the retinal sensitivity map is shown imposed on the SLO fundus image, with absolute scotoma over the area of geographic atrophy. On the right side of the same retinal sensitivity map, the fixation assessment shows stable central fixation with 92% of the fixation points lying within the central 28 circle. The image was acquired by the authors at the Diagnostic Center at the Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA. OCT, optical coherence tomography; SLO, scanning laser ophthalmoscope.
multiple coalescent areas of loss of the retinal pigment epithelium in patients with macular drusen [39]. Geographic atrophy is the hallmark clinical finding of the advanced form of nonexudative AMD and is acknowledged to account for 20% of the legal blindness attributed to AMD in North America [40]. Characteristically, loss of photoreceptor layer, retinal pigment epithelium, and choriocapillaries in geographic atrophy starts parafoveally leading to parafoveal scotomas and dysfunction of rods and cones interfering with the daily activities of the patient such as reading and driving. Eventually, geographic atrophy progresses to the fovea leading to profound effect on central visual acuity [41,42]. At present, there is no known effective treatment that can reverse the detrimental effects of geographic atrophy or halt its progression [43]. The gradual time-dependent change in the area of geographic atrophy lesion(s) is a key feature that has been closely studied using wide variety of imaging modalities including digital fundus photography, fundus 152
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autofluorescence, and optical coherence tomography [26,44,45]. Examination of the functional loss associated with increase in geographic atrophy area may help toward more comprehensive understanding of the disease process. Best-corrected visual acuity does not correlate reliably with geographic atrophy progression and does not reflect the actual visual disability. Patients with geographic atrophy have shown reduction in low-luminance visual acuity, contrast sensitivity, and reading speed in previous studies [46,47]. However, the temporal changes in these measurements and its correlation with anatomic change have never been fully investigated. With its ability to produce precise and repeatable mapped measurements of retinal sensitivities, microperimetry may represent the optimal potential imaging modality that may close the loop between anatomic and functional evaluation in geographic atrophy, specifically, and macular degenerative disorders, in general. At present, the role of Volume 26 Number 3 May 2015
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Introduction to microperimetry and its role in analysis of geographic atrophy Hanout et al.
microperimetry in degenerative macular disease with geographic atrophy is being heavily researched. There are numerous clinical trials exploring different treatment modalities for macular degeneration, and microperimetry imaging has become a mainstay in monitoring the disease progress. Microperimetry has been recently utilized in a phase I trial looking at autologous bone marrow cells in the restoration of retinal tissue [48]. It was also employed in another phase I/II trial investigating the effects of intravitreal sirolimus in geographic atrophy [49]. Furthermore, a phase I trial also used microperimetry to evaluate safety of intraocular delivery of ciliary neurotrophic factor for macular telangiectasia type 2 [50]. These studies are far from the only ones, but they portray the wide variety of studies investigating new treatments for macular diseases, all incorporate the use of microperimetry to monitor treatment effectiveness.
ASSESSMENT OF MACULAR SENSITIVITY IN GEOGRAPHIC ATROPHY A decline in macular sensitivity and increase in macular scotoma has been observed in clinical studies of geographic atrophy. In a study that followed nine patients with bilateral geographic atrophy for 24 months to evaluate the change in retinal sensitivity, a general trend of decreasing retinal sensitivity was observed in the overall tested area, including areas outside the geographic atrophy lesion. Furthermore, all eyes demonstrated an overall increase in the number of points with absolute scotoma during the follow-up period [23]. In another study, microperimetry was used to examine retinal sensitivity in areas with nascent geographic atrophy compared with nonatrophic areas in 24 eyes with intermediate AMD. Areas of nascent geographic atrophy showed worse retinal sensitivity compared with nonatrophic areas, but better retinal sensitivity compared with areas of drusen-associated atrophy as detected on spectral domain OCT [24 ]. &
EXTRAFOVEAL FIXATION AND PREFERRED RETINAL LOCUS Geographic atrophy will eventually result in retinal damage and irreversible loss of central vision. Consequently, several functional adaptation strategies will develop to compensate for the resultant visual disability and enhance the residual functional vision [51]. A key adaptive mechanism is to develop an eccentric retinal area with preserved visual function, and is physically close to, commonly at the superior border of [52], the lost fovea so that it
assumes foveal function. Early in the adaptation process, multiple loci in the retina may be recruited and become preferred over all other retinal areas for the higher visual tasks. In addition, those loci show greater potential to improve in functionality with training, become more repeatedly aligned with visual targets, and become used as oculomotor reference. Such retinal areas are referred to as PRLs [53,54]. Later in the adaptation process, usually a single PRL takes over eccentric visual function and becomes the only functional retinal locus with well established location in the retina [53]. Before the advent of the SLO, PRL was crudely identified by clinical observation. Microperimeters offer optimal instrumentation to detect the precise topographic location of the PRL and its orientation from the old fovea. The PRL appears on microperimetry as a circumscribed area in the retina covered with fixation points [52]. The orientation of the PRL from the old fovea can be expressed and documented in degrees of eccentricity, which is essential for research studies and disease monitoring in clinical setting [8].
FIXATION STABILITY The second crucial component of the natural adaptation process that follows irreversible central vision loss in geographic atrophy encompasses improving the fixation stability in the new PRL to achieve better visual function. This process is modulated through the oculomotor function [8]. Fixation stability, may also be referred to as fixation quality, is defined as the ability of the eye to maintain fixation in the PRL. Fixation would be considered stable if 75% or more of fixation points fall within 28 diameter circle; relatively unstable if less 75% are inside the 28 diameter circle but more than 75% fall inside the 48 diameter circle; and unstable if less than 75% of the fixation points are inside the 48 diameter circle [27]. Fixation stability can also be assessed by measuring the area covered by the fixation points in square degrees, referred to as the bicurve ellipse area (BCEA) (Fig. 2), which can be accurately estimated using microperimetry. BCEA is calculated from the minor and major axes of an ellipse area covering fixational eye movements, accounting for 2 standard deviations (SDs) of recorded eye movements. A recent study showed the mean BCEA to be 0.05382 (SD ¼ 0.022) in normal eyes and 6.7682 (SD ¼ 8.36; range, 0.21–31.858) in eyes with AMD, respectively [55]. In a recent study that followed patients with geographic atrophy for 24 months using of microperimetry, decreases in mean fixation quality were observed for both measures using the 28 and 48
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FIGURE 2. Results of microperimetric examination of the left eye of a patient with geographic atrophy using Nidek MP-1 Microperimeter (Nidek Technologies, Padova, Italy). Retinal sensitivity map shows several points with absolute scotoma over the geographic atrophy area. The BCEA is enlarged measuring 4.1 degrees square (4.182). Normal BCEA is reported to be 0.05382 (SD ¼ 0.02282). Fixation is labeled as ‘relatively unstable’, as shown in the panel on the top left corner, with only 57% of the fixation points within the central 28 circle, but with 92% of the fixation points within the central 48 circle. Testing parameters were: stimulus size ¼ Goldmann III, duration ¼ 200 ms, and strategy ¼ 4-2, pattern ¼ 10-2 68 points. The image was acquired by the authors at the Diagnostic Center at the Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA. BCEA, bicurve ellipse area; SD, standard deviation.
circles over the study duration with the mean percentage of fixation positions located within the 28 circle decreasing by 11.9% per year, and that located within the 48circle decreasing by 11.7% per year [23]. In addition, at 24 months, 16.6% of eyes labeled to have ‘stable fixation’ at baseline progressed to ‘relatively unstable’, and 60% of eyes labeled ‘relatively unstable’ at baseline progressed to ‘unstable’. None of the enrolled eyes evaluated in the study demonstrated an improvement in fixation stability throughout the 24-months follow-up period [23].
RELIABILITY OF MICROPERIMETRY RETEST IN GEOGRAPHIC ATROPHY Test–retest reliability has been an area of discussion when looking at the clinical implications of microperimetry in patients with geographic atrophy in 154
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AMD, and there are multiple psychophysical factors affecting variability in clinical trials being performed currently. Learning effect commonly takes place between the first and second test. Regardless of the condition of the individual patient, it has frequently been shown that the patient will show perceived improvement upon repeated examination [56 ]. It has been recommended to automatically discount the first test and to count the repeated one as baseline to combat this effect. Other aspects of study design need to be accounted for, such as adaptation when performing examinations on one eye immediately after the other, experience of the operator of the machine, and timing between tests [56 ]. There are different parameters for the measurements of microperimetry including macular mean sensitivity, macular mean deviation, and pointwise sensitivity [57]. Mean sensitivity and mean &&
&&
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Introduction to microperimetry and its role in analysis of geographic atrophy Hanout et al.
deviation are averages of retinal sensitivities and do not portray local changes or progression of disease. Conversely, pointwise sensitivity looks at all loci but has been shown to have higher variability. Moreover, it may also have ceiling and floor effects in microperimeters with relatively narrow range of luminance such as Nidek MP-1 [57]. Another issue in reliability is the possible fixation of different landmarks on the retina in different tests [13].
CONCLUSION There is increasing evidence supporting the usefulness of microperimetry as a clinical and research tool. In advanced diseases associated with permanent loss of central vision, such as geographic atrophy, best-corrected visual acuity and other psychophysical tests, including low-luminance visual acuity, reading speed, and contrast sensitivity, may not represent the actual visual disability of the patient. Microperimetry, garnished by real-time eye-tracking technology and precise assessment of the location and stability of fixation, may provide optimal evaluation of the residual visual function. This technology can also assist in attempts to restore functional vision and improve quality of life when employed as training tool in low vision rehabilitation programs. Progression of functional decline in geographic atrophy as observed in clinical studies may involve enlargement of absolute scotoma, decrease in retinal sensitivity surrounding geographic atrophy lesion(s), and loss of fixation stability. These trends may call for incorporating microperimetry as a standard functional outcome measure in clinical trials for geographic atrophy. Acknowledgements None. Financial support and sponsorship D.V.D. has received research funding from Genentech and Regeneron. Conflicts of interest There are no conflicts of interest.
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43. Lindblad AS, Lloyd PC, Clemons TE, et al. Change in area of geographic atrophy in the age-related eye disease study: AREDS report number 26. Arch Ophthalmol 2009; 127:1168–1174. 44. Holz FG, Bellman C, Staudt S, et al. Fundus autofluorescence and development of geographic atrophy in age-related macular degeneration. Investig Ophthalmol Vis Sci 2001; 42:1051–1056. 45. Fleckenstein M, Schmitz-Valckenberg S, Adrion C, et al. Tracking progression with spectral-domain optical coherence tomography in geographic atrophy caused by age-related macular degeneration. Investig Ophthalmol Vis Sci 2010; 51:3846–3852. 46. Sunness JS, Rubin GS, Broman A, et al. Low luminance visual dysfunction as a predictor of subsequent visual acuity loss from geographic atrophy in agerelated macular degeneration. Ophthalmology 2008; 115:1480–1488. 47. Sunness JS, Applegate CA, Haselwood D, Rubin GS. Fixation patterns and reading rates in eyes with central scotomas from advanced atrophic agerelated macular degeneration and Stargardt disease. Ophthalmology 1996; 103:1458–1466. 48. Park SS, Bauer G, Abedi M, et al. Intravitreal autologous bone marrow CD34þ cell therapy for ischemic and degenerative retinal disorders: preliminary phase 1 clinical trial findings. Investig Ophthalmol Vis Sci 2014; 56:81–89. 49. Petrou PA, Cunningham D, Shimel K, et al. Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial. Investig Ophthalmol Vis Sci 2015; 56:330–338. 50. Chew EY, Clemons TE, Peto T, et al. Ciliary neurotrophic factor for macular telangiectasia type 2: results from a phase 1 safety trial. Am J Ophthalmol 2014; 14:00819-8. 51. Cheung SH, Legge GE. Functional and cortical adaptations to central vision loss. Vis Neurosci 2005; 22:187–201. 52. Fletcher DC, Schuchard RA. Preferred retinal loci relationship to macular scotomas in a low-vision population. Ophthalmology 1997; 104:632–638. 53. Shima N, Markowitz SN, Reyes SV. Concept of a functional retinal locus in age-related macular degeneration. Can J Ophthalmol 2010; 45:62–66. 54. Crossland MD, Engel SA, Legge GE. The preferred retinal locus in macular disease: toward a consensus definition. Retina (Philadelphia, PA) 2011; 31:2109–2114. 55. Tarita-Nistor L, Gonzalez EG, Markowitz SN, Steinbach MJ. Fixation characteristics of patients with macular degeneration recorded with the mp-1 microperimeter. Retina (Philadelphia, PA) 2008; 28:125–133. 56. Wu Z, Ayton LN, Guymer RH, Luu CD. Intrasession test-retest variability of && microperimetry in age-related macular degeneration. Investig Ophthalmol Vis Sci 2013; 54:7378–7385. This study highlights the ‘learning effect’ that develops after the first microperimetric examination leading to marked better sensitivity in the second examination. This concludes that discarding the first microperimetric examination of the patient will reflect more accurate microperimetric evaluation in the following examinations. 57. Chen FK, Patel PJ, Xing W, et al. Test-retest variability of microperimetry using the Nidek MP1 in patients with macular disease. Investig Ophthalmol Vis Sci 2009; 50:3464–3472.
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Introduction to microperimetry and its use in analysis of geographic atrophy in age-related macular degeneration Mostafa Hanout, Nicholas Horan, and Diana V. Do
Purpose of review This article discusses recent advances in the fundus-guided perimetry (microperimetry) and its utilization in evaluation and monitoring of patients with geographic atrophy. Recent findings Although best-corrected visual acuity has been gold standard in clinical practice for decades, it does not provide an entire assessment of visual function that determines daily activity and quality of life of a patient. Furthermore, psychophysical tests, including low-luminance visual acuity, reading speed, and contrast sensitivity, cannot be used to quantify retinal sensitivity or detect pattern of retinal dysfunction. Microperimetry provides a true evaluation of visual function by offering fundus-controlled testing through eye-tracking technology that allows for structural and functional correlation and test–retest reliability for the same test point. Furthermore, it enables precise assessment of location and stability of fixation. Recent research has shown microperimetry to be more representative of the macular function in macular diseases. Summary Microperimetry is currently the clinical investigation of choice to assess residual visual functions and functional vision in macular degenerative diseases, especially geographic atrophy. There is an increasing popularity to employ microperimetry in clinical trials investigating new treatments for geographic atrophy, as well as other macular degenerative diseases, as a reliable functional outcome measure. Keywords fixation, geographic atrophy, microperimetry, preferred retinal locus, retinal sensitivity
INTRODUCTION The advances in retinal imaging technologies have revolutionized contemporary diagnostic in ophthalmology and enabled early detection along with documentation of treatment results of retinal diseases. Precise clinical evaluation of retinal, especially macular involving, diseases necessitates correlating both the morphological and the functional aspects. The latter is more self-appreciated by patients, as major visual tasks determining the quality of life of patient grossly depend on it [1]. For decades, best-corrected visual acuity has been the gold standard in clinical practice; however, it does not represent an entire assessment of macular function. There are several puzzling presentations by patients whose visual function is inconsistent with visual acuity such as patients with paracentral macular lesions sparing the foveal center. Several psychophysical tests have been utilized, in addition to visual acuity, to evaluate macular function such as Amsler grid, contrast sensitivity, reading speed, and
low-luminance visual acuity among others. However, none of these testing parameters has proved ability to quantify retinal sensitivity or detect pattern of retinal dysfunction [2–4]. For many years, conventional static perimetry has been established as an essential clinical tool for quantification of visual field and retinal threshold especially in glaucoma and neuro-ophthalmological disorders. Nonetheless, it is often inadequate for accurate evaluation of macular function, especially with troublesome eccentric or unsteady fixation, or both [1,5,6].
Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA Correspondence to Diana V. Do, MD, Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, 985540 Nebraska Medical Center, Omaha, NE 68198-5540, USA. Tel: +1 402 559 4276; fax: +1 402 559 5514; e-mail: [email protected] Curr Opin Ophthalmol 2015, 26:149–156 DOI:10.1097/ICU.0000000000000153
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Retinal, vitreous and macular disorders
KEY POINTS Best-corrected visual acuity, psychophysical tests, and conventional perimetry, albeit useful, do not fulfill the desired comprehensive assessment of macular function in macular degenerative diseases. Residual visual function has more impact on the patient daily activity and quality of life. Microperimetry is currently the clinical investigation of choice to assess residual visual functions and functional vision in macular degenerative diseases, especially geographic atrophy. Microperimetry offers fundus-controlled testing of retinal sensitivity through eye-tracking technology that allows for structural and functional correlation and test–retest reliability for the same test point. Furthermore, it enables precise assessment of location and stability of fixation. Recent trends may call for incorporating microperimetry as a standard functional outcome measure in clinical trials of geographic atrophy.
More recently, microperimetry has effectively provided fundus-correlated functional testing, test–retest reliability for the same test point, precise assessment of the location and stability of fixation, and compensation for ocular movements. By incorporating these features, microperimetry has become the clinical investigation of choice to assess residual visual functions and functional vision in macular diseases [7,8]. This article covers basic concepts and recent advances in microperimetry, common marketavailable microperimeters, and the steadily growing role of microperimetry in clinical evaluation and monitoring of macular diseases, particularly, geographic atrophy. Latest research observations reported during the review period are also summarized.
fundus observation during examination [9]. The main challenge was that the bright light necessary for adequate retinal illumination will interfere with functional testing. With the advent of scanning laser ophthalmoscope (SLO), the infrared light source permitted simultaneous observation of the fundus during examination and led to introduction of the first microperimeter (SLO 101, Rodenstock, Ottobrunn, Germany) in the year 1982 [9,10]. Shortcomings of this device included semiautomated stimulus presentation and lack of eye tracker to compensate for ocular movements; the device is no longer available in the market. These limitations have been overcome by Nidek MP-1 (Nidek Technologies, Padova, Italy) that was introduced to the market in 2003 as the first fundus perimeter with eye tracker that compensates for eye movements based on an initial frame. With these new features in Nidek MP-1, exact correlation between retinal disorder and functional defects was rendered possible even in eyes with poor or unstable fixation [11,12 ,13,14]. Thereafter, in 2006, a more recent Spectral OCT/SLO microperimeter was introduced to the market by OPKO/OTI (OPKO Instrumentation, Miami, Florida, USA) that incorporated spectral optical coherence tomography (OCT) with microperimetry, offering an additional advantage of correlating retinal dysfunction with the corresponding ultrastructural finding as shown by OCT. The technology was later transferred to Optos Inc., and the device was named Optos OCT/SLO (Optos, Dunfermline, Scotland, UK). Optos OCT/ SLO is the only US Food and Drug Administration-approved microperimeter; it received 510(k) clearance in 2013 [3,15–18]. Macular Integrity Assessment (MAIA; CenterVue, Padova, Italy) was the latest instrument to reach the market in 2009, garnished with high-frequency eye tracker and a line confocal SLO [6,7]. Table 1 summarizes key differences between the three commercially available microperimeters. &
EVOLUTION OF MICROPERIMETRY According to many experts in the field, ‘microperimetry’ is not the most accurate naming for this ocular imaging technology, given the currently used examination parameters of stimulus size ranging from Goldman I to V, and examination field of up to 158–208 from the foveal center. Rather, ‘fundus-correlated perimetry’ or ‘fundus-guided perimetry’ are considered more accurate names. For sake of simplicity, we used the term ‘microperimetry’ throughout the article [5,6]. The need to achieve correlation between clinically apparent retinal disorder and functional testing urged the demand to design a perimetry device that enables 150
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CLINICAL APPLICATIONS OF MICROPERIMETRY Indeed, microperimetry surpasses conventional perimetry in several aspects in evaluation of retinal sensitivity in macular diseases [19]. One fundamental advantage of microperimetry is the real-time tracking of the fundus throughout perimetric testing. This allows perimetric examination of patients with eccentric or unstable fixation. The ability of registration of macular sensitivity results on digital fundus photograph allows for functional and structural correlation [6]. Furthermore, in conventional perimetry, the stimulus is projected on a screen in front Volume 26 Number 3 May 2015
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Introduction to microperimetry and its role in analysis of geographic atrophy Hanout et al. Table 1. Summary of commercially available microperimeters
Manufacturer
Nidek MP-1
Optos OCT/SLO
MAIA
Nidek Technologies, Padova, Italy
Optos, Dunfermline, Scotland, UK
CenterVue, Padova, Italy
Year of arrival to the market
2003
2006
2009
Features of incorporated fundus imaging
Infrared and digital color
SLO black and white
SLO black and white
458
29.78
368
Fixation assessment
Eye-tracking technology
SLO
High-frequency eye tracker
Background luminance
1.27 cd/m2
10 cd/m2
Microperimetric examination parameters Size of the of the microperimetry testing field
2
1.27 cd/m2 2
Highest stimulus intensity
128 cd/m
125 cd/m
318 cd/m2
Dynamic range of stimulus attenuation
0–20 dB
0–20 dB
0–36 dB
Coregistration of retinal sensitivity map on the fundus image
Automatic or Manual Options
Automatic with simultaneous SLO and OCT
Automatic coregistration
Advantages and unique features
Continuous fundus autofocus
Combined OCT for structural and functional correlation
High-resolution fundus imaging 1024 1024
Automatic retest
Available
Available
Available
Biofeedback training
Biofeedback training
MAIA, Macular Integrity Assessment; OCT, optical coherence tomography; SLO, scanning laser ophthalmoscope.
of the patient’s eye, whereas in microperimetry, the stimulus is directly projected on the predefined retinal points helped with the eye-tracking technology. This is another key advantage that allows for accurate test–retest of the same point in microperimetry with a shift range of about 0.538. On the other hand, sensitivity of a given point in conventional perimetry represents, in fact, the average of an area of about 58 [8]. The development of multiple commercially available microperimeters, such as Nidek MP-1, Optos OCT/SLO, and MAIA, has led to widespread use of microperimetry and allowed thorough evaluation of the device in clinical studies. Since late 80th of the last Century, microperimetry has been investigated in enormous number of clinical studies. It was shown to play a great role in diagnosis and follow-up of myriad of retinal and macular disorders including age-related macular degeneration (AMD) [20,21], geographic atrophy [22,23,24 ,25,26], choroidal neovascularization [27], diabetic retinopathy [15–17,28], uveitic macular edema [29–31], central serous chorioretinopathy [32], and macular dystrophies such as Stargardt’s disease [33] and North Carolina dystrophy [34]. Moreover, it has been instrumental in evaluating treatment results of several pharmacological therapies, as well as laser and surgical procedures. Examples include intravitreal antivascular endothelial growth factor for treating neovascular AMD [35], retinal laser photocoagulation for diabetic macular edema [36], and pars plana vitrectomy for macular holes [37,38]. There is no &
doubt that this innovative imaging modality, microperimetry, has significantly increased our knowledge and understanding of many macular disorders. For instance, microperimetry revealed the presence of dense scotomas over macular holes [37] and over macular areas where there is loss of integrity in the inner segment/outer segment layer [15]. Similarly, detecting the shift of preferred retinal locus (PRL) from the foveal center to the intact retina superior to central scotomas in macular holes or paracentral scotomas in number of other macular dystrophies would have not been possible without microperimetry [5]. In general, clinicians and researchers should be familiar with the features of different commercially available microperimeters so that they can select the version that services their purposes. For instance, Optos OCT/SLO may be the best choice for retina specialists practicing medical and surgical retina as it combines OCT with microperimetry (Fig. 1). On the other hand, those who practice low vision rehabilitation for patients with macular degenerative diseases such as geographic atrophy will benefit from the biofeedback training module in Nidek MP-1 and MAIA.
ROLE OF MICROPERIMETRY IN ANALYSIS OF GEOGRAPHIC ATROPHY The term ‘geographic atrophy’ was devised by the pioneer J. Donald M. Gass in 70th of the last century who first used it to describe discrete single or
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FIGURE 1. Combination of functional assessment using microperimetry and morphological assessment using OCT are combined in the Optos OCT/SLO Microperimeter (Optos, Dunfermline, Scotland, UK). The retinal sensitivity grid is imposed on the fundus image. The horizontal (blue line) and the vertical (green line) OCT scans crosses at one point that shows an absolute scotoma (0 dB). This enables precise structural and functional evaluation of the exact location in the fundus. In the bottom right corner of the image, the retinal sensitivity map is shown imposed on the SLO fundus image, with absolute scotoma over the area of geographic atrophy. On the right side of the same retinal sensitivity map, the fixation assessment shows stable central fixation with 92% of the fixation points lying within the central 28 circle. The image was acquired by the authors at the Diagnostic Center at the Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA. OCT, optical coherence tomography; SLO, scanning laser ophthalmoscope.
multiple coalescent areas of loss of the retinal pigment epithelium in patients with macular drusen [39]. Geographic atrophy is the hallmark clinical finding of the advanced form of nonexudative AMD and is acknowledged to account for 20% of the legal blindness attributed to AMD in North America [40]. Characteristically, loss of photoreceptor layer, retinal pigment epithelium, and choriocapillaries in geographic atrophy starts parafoveally leading to parafoveal scotomas and dysfunction of rods and cones interfering with the daily activities of the patient such as reading and driving. Eventually, geographic atrophy progresses to the fovea leading to profound effect on central visual acuity [41,42]. At present, there is no known effective treatment that can reverse the detrimental effects of geographic atrophy or halt its progression [43]. The gradual time-dependent change in the area of geographic atrophy lesion(s) is a key feature that has been closely studied using wide variety of imaging modalities including digital fundus photography, fundus 152
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autofluorescence, and optical coherence tomography [26,44,45]. Examination of the functional loss associated with increase in geographic atrophy area may help toward more comprehensive understanding of the disease process. Best-corrected visual acuity does not correlate reliably with geographic atrophy progression and does not reflect the actual visual disability. Patients with geographic atrophy have shown reduction in low-luminance visual acuity, contrast sensitivity, and reading speed in previous studies [46,47]. However, the temporal changes in these measurements and its correlation with anatomic change have never been fully investigated. With its ability to produce precise and repeatable mapped measurements of retinal sensitivities, microperimetry may represent the optimal potential imaging modality that may close the loop between anatomic and functional evaluation in geographic atrophy, specifically, and macular degenerative disorders, in general. At present, the role of Volume 26 Number 3 May 2015
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Introduction to microperimetry and its role in analysis of geographic atrophy Hanout et al.
microperimetry in degenerative macular disease with geographic atrophy is being heavily researched. There are numerous clinical trials exploring different treatment modalities for macular degeneration, and microperimetry imaging has become a mainstay in monitoring the disease progress. Microperimetry has been recently utilized in a phase I trial looking at autologous bone marrow cells in the restoration of retinal tissue [48]. It was also employed in another phase I/II trial investigating the effects of intravitreal sirolimus in geographic atrophy [49]. Furthermore, a phase I trial also used microperimetry to evaluate safety of intraocular delivery of ciliary neurotrophic factor for macular telangiectasia type 2 [50]. These studies are far from the only ones, but they portray the wide variety of studies investigating new treatments for macular diseases, all incorporate the use of microperimetry to monitor treatment effectiveness.
ASSESSMENT OF MACULAR SENSITIVITY IN GEOGRAPHIC ATROPHY A decline in macular sensitivity and increase in macular scotoma has been observed in clinical studies of geographic atrophy. In a study that followed nine patients with bilateral geographic atrophy for 24 months to evaluate the change in retinal sensitivity, a general trend of decreasing retinal sensitivity was observed in the overall tested area, including areas outside the geographic atrophy lesion. Furthermore, all eyes demonstrated an overall increase in the number of points with absolute scotoma during the follow-up period [23]. In another study, microperimetry was used to examine retinal sensitivity in areas with nascent geographic atrophy compared with nonatrophic areas in 24 eyes with intermediate AMD. Areas of nascent geographic atrophy showed worse retinal sensitivity compared with nonatrophic areas, but better retinal sensitivity compared with areas of drusen-associated atrophy as detected on spectral domain OCT [24 ]. &
EXTRAFOVEAL FIXATION AND PREFERRED RETINAL LOCUS Geographic atrophy will eventually result in retinal damage and irreversible loss of central vision. Consequently, several functional adaptation strategies will develop to compensate for the resultant visual disability and enhance the residual functional vision [51]. A key adaptive mechanism is to develop an eccentric retinal area with preserved visual function, and is physically close to, commonly at the superior border of [52], the lost fovea so that it
assumes foveal function. Early in the adaptation process, multiple loci in the retina may be recruited and become preferred over all other retinal areas for the higher visual tasks. In addition, those loci show greater potential to improve in functionality with training, become more repeatedly aligned with visual targets, and become used as oculomotor reference. Such retinal areas are referred to as PRLs [53,54]. Later in the adaptation process, usually a single PRL takes over eccentric visual function and becomes the only functional retinal locus with well established location in the retina [53]. Before the advent of the SLO, PRL was crudely identified by clinical observation. Microperimeters offer optimal instrumentation to detect the precise topographic location of the PRL and its orientation from the old fovea. The PRL appears on microperimetry as a circumscribed area in the retina covered with fixation points [52]. The orientation of the PRL from the old fovea can be expressed and documented in degrees of eccentricity, which is essential for research studies and disease monitoring in clinical setting [8].
FIXATION STABILITY The second crucial component of the natural adaptation process that follows irreversible central vision loss in geographic atrophy encompasses improving the fixation stability in the new PRL to achieve better visual function. This process is modulated through the oculomotor function [8]. Fixation stability, may also be referred to as fixation quality, is defined as the ability of the eye to maintain fixation in the PRL. Fixation would be considered stable if 75% or more of fixation points fall within 28 diameter circle; relatively unstable if less 75% are inside the 28 diameter circle but more than 75% fall inside the 48 diameter circle; and unstable if less than 75% of the fixation points are inside the 48 diameter circle [27]. Fixation stability can also be assessed by measuring the area covered by the fixation points in square degrees, referred to as the bicurve ellipse area (BCEA) (Fig. 2), which can be accurately estimated using microperimetry. BCEA is calculated from the minor and major axes of an ellipse area covering fixational eye movements, accounting for 2 standard deviations (SDs) of recorded eye movements. A recent study showed the mean BCEA to be 0.05382 (SD ¼ 0.022) in normal eyes and 6.7682 (SD ¼ 8.36; range, 0.21–31.858) in eyes with AMD, respectively [55]. In a recent study that followed patients with geographic atrophy for 24 months using of microperimetry, decreases in mean fixation quality were observed for both measures using the 28 and 48
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FIGURE 2. Results of microperimetric examination of the left eye of a patient with geographic atrophy using Nidek MP-1 Microperimeter (Nidek Technologies, Padova, Italy). Retinal sensitivity map shows several points with absolute scotoma over the geographic atrophy area. The BCEA is enlarged measuring 4.1 degrees square (4.182). Normal BCEA is reported to be 0.05382 (SD ¼ 0.02282). Fixation is labeled as ‘relatively unstable’, as shown in the panel on the top left corner, with only 57% of the fixation points within the central 28 circle, but with 92% of the fixation points within the central 48 circle. Testing parameters were: stimulus size ¼ Goldmann III, duration ¼ 200 ms, and strategy ¼ 4-2, pattern ¼ 10-2 68 points. The image was acquired by the authors at the Diagnostic Center at the Stanley M. Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska, USA. BCEA, bicurve ellipse area; SD, standard deviation.
circles over the study duration with the mean percentage of fixation positions located within the 28 circle decreasing by 11.9% per year, and that located within the 48circle decreasing by 11.7% per year [23]. In addition, at 24 months, 16.6% of eyes labeled to have ‘stable fixation’ at baseline progressed to ‘relatively unstable’, and 60% of eyes labeled ‘relatively unstable’ at baseline progressed to ‘unstable’. None of the enrolled eyes evaluated in the study demonstrated an improvement in fixation stability throughout the 24-months follow-up period [23].
RELIABILITY OF MICROPERIMETRY RETEST IN GEOGRAPHIC ATROPHY Test–retest reliability has been an area of discussion when looking at the clinical implications of microperimetry in patients with geographic atrophy in 154
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AMD, and there are multiple psychophysical factors affecting variability in clinical trials being performed currently. Learning effect commonly takes place between the first and second test. Regardless of the condition of the individual patient, it has frequently been shown that the patient will show perceived improvement upon repeated examination [56 ]. It has been recommended to automatically discount the first test and to count the repeated one as baseline to combat this effect. Other aspects of study design need to be accounted for, such as adaptation when performing examinations on one eye immediately after the other, experience of the operator of the machine, and timing between tests [56 ]. There are different parameters for the measurements of microperimetry including macular mean sensitivity, macular mean deviation, and pointwise sensitivity [57]. Mean sensitivity and mean &&
&&
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Introduction to microperimetry and its role in analysis of geographic atrophy Hanout et al.
deviation are averages of retinal sensitivities and do not portray local changes or progression of disease. Conversely, pointwise sensitivity looks at all loci but has been shown to have higher variability. Moreover, it may also have ceiling and floor effects in microperimeters with relatively narrow range of luminance such as Nidek MP-1 [57]. Another issue in reliability is the possible fixation of different landmarks on the retina in different tests [13].
CONCLUSION There is increasing evidence supporting the usefulness of microperimetry as a clinical and research tool. In advanced diseases associated with permanent loss of central vision, such as geographic atrophy, best-corrected visual acuity and other psychophysical tests, including low-luminance visual acuity, reading speed, and contrast sensitivity, may not represent the actual visual disability of the patient. Microperimetry, garnished by real-time eye-tracking technology and precise assessment of the location and stability of fixation, may provide optimal evaluation of the residual visual function. This technology can also assist in attempts to restore functional vision and improve quality of life when employed as training tool in low vision rehabilitation programs. Progression of functional decline in geographic atrophy as observed in clinical studies may involve enlargement of absolute scotoma, decrease in retinal sensitivity surrounding geographic atrophy lesion(s), and loss of fixation stability. These trends may call for incorporating microperimetry as a standard functional outcome measure in clinical trials for geographic atrophy. Acknowledgements None. Financial support and sponsorship D.V.D. has received research funding from Genentech and Regeneron. Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Midena E. Microperimetry. Arch Soc Espanola Oftalmol 2006; 81:183–186. 2. McClure ME, Hart PM, Jackson AJ, et al. Macular degeneration: do conventional measurements of impaired visual function equate with visual disability? Br J Ophthalmol 2000; 84:244–250.
3. Liu H, Bittencourt MG, Wang J, et al. Assessment of central retinal sensitivity employing two types of microperimetry devices. Transl Vis Sci Technol 2014; 3:3. 4. Do DV. Detection of new-onset choroidal neovascularization. Curr Opin Ophthalmol 2013; 24:244–247. 5. Rohrschneider K, Bultmann S, Springer C. Use of fundus perimetry (microperimetry) to quantify macular sensitivity. Prog Retinal Eye Res 2008; 27:536–548. 6. Acton JH, Greenstein VC. Fundus-driven perimetry (microperimetry) compared to conventional static automated perimetry: similarities, differences, and clinical applications. Can J Ophthalmol 2013; 48:358–363. 7. Markowitz SN. Microperimeters and microperimetry: new technology in ophthalmology with far-reaching applications. Can J Ophthalmol 2013; 48:347–348. 8. Markowitz SN, Reyes SV. Microperimetry and clinical practice: an evidencebased review. Can J Ophthalmol 2013; 48:350–357. 9. Enoch JM. Quantitative layer-by-layer perimetry: an update. Am J Optometry Physiol Optics 1982; 59:952–953. 10. Timberlake GT, Mainster MA, Webb RH, et al. Retinal localization of scotomata by scanning laser ophthalmoscopy. Investig Ophthalmol Vis Sci 1982; 22:91–97. 11. Midena E, Vujosevic S, Cavarzeran F; Microperimetry Study Group. Normal values for fundus perimetry with the microperimeter MP1. Ophthalmology 2010; 117:1571–1576. 12. Seiple W, Rosen RB, Castro-Lima V, Garcia PM. The physics and psycho& physics of microperimetry. Optometry Vis Sci 2012; 89:1182–1191. This study looked at the effect of change in stimulus parameters on the measurement of retinal sensitivity. It investigated three commonly used devices: Humphrey field analyzer, which is a conventional static perimeter, Nidek MP-1, which is the first commercial microperimeter with true eye tracking and the most frequently studied in research, and Optos OCT/SLO, which is the only microperimeter combining OCT. It highlighted the importance of awareness of the psychophysical parameters incorporated by each manufacturer and the necessity of this information for clinicians for precise interpretation of retinal sensitivity testing. 13. Chen FK, Patel PJ, Xing W, et al. Intrasession repeatability of fixation stability assessment with the Nidek MP-1. Optometry Vis Sci 2011; 88:742–750. 14. Chen FK, Patel PJ, Webster AR, et al. Nidek MP1 is able to detect subtle decline in function in inherited and age-related atrophic macular disease with stable visual acuity. Retina (Philadelphia, PA) 2011; 31:371–379. 15. Yohannan J, Bittencourt M, Sepah YJ, et al. Association of retinal sensitivity to integrity of photoreceptor inner/outer segment junction in patients with diabetic macular edema. Ophthalmology 2013; 120:1254–1261. 16. Hatef E, Hanout M, Moradi A, et al. Longitudinal comparison of visual acuity as measured by the ETDRS chart and by the potential acuity meter in eyes with macular edema, and its relationship with retinal thickness and sensitivity. Eye (London, England) 2014; 28:1239–1245. 17. Hatef E, Colantuoni E, Wang J, et al. The relationship between macular sensitivity and retinal thickness in eyes with diabetic macular edema. Am J Ophthalmol 2011; 152:400–405. 18. Shulman M, Sepah YJ, Chang S, et al. Management of retained subretinal perfluorocarbon liquid. Ophthal Surg Lasers Imag Retina 2013; 44:577– 583. 19. Markowitz SN. Visual function in glaucoma. Ophthalmology 2011; 118:2528–2529. 20. Sabates NR, Crane WG, Sabates FN, et al. Scanning laser ophthalmoscope macular perimetry in the evaluation of submacular surgery. Retina (Philadelphia, PA) 1996; 16:296–304. 21. Rohrschneider K, Gluck R, Becker M, et al. Scanning laser fundus perimetry before laser photocoagulation of well defined choroidal neovascularisation. Br J Ophthalmol 1997; 81:568–573. 22. Schmitz-Valckenberg S, Bultmann S, Dreyhaupt J, et al. Fundus autofluorescence and fundus perimetry in the junctional zone of geographic atrophy in patients with age-related macular degeneration. Investig Ophthalmol Vis Sci 2004; 45:4470–4476. 23. Meleth AD, Mettu P, Agron E, et al. Changes in retinal sensitivity in geographic atrophy progression as measured by microperimetry. Investig Ophthalmol Vis Sci 2011; 52:1119–1126. 24. Wu Z, Ayton LN, Luu CD, Guymer RH. Microperimetry of nascent geographic & atrophy in age-related macular degeneration. Investig Ophthalmol Vis Sci 2014; 56:115–121. This study used microperimetry to compare retinal sensitivity of the nascent geographic atrophy, drusen-associated geographic atrophy, and nonpathologic retinal areas. It showed that the areas of nascent geographic atrophy, although showed worse sensitivity compared with normal retina, showed better sensitivity than drusen-associated geographic atrophy. It furthers the understanding of the pathological changes in an intermediate stage of AMD prior to development of geographic atrophy. 25. Sunness JS, Bressler NM, Maguire MG. Scanning laser ophthalmoscopic analysis of the pattern of visual loss in age-related geographic atrophy of the macula. Am J Ophthalmol 1995; 119:143–151. 26. Sunness JS, Bressler NM, Tian Y, et al. Measuring geographic atrophy in advanced age-related macular degeneration. Investig Ophthalmol Vis Sci 1999; 40:1761–1769.
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Volume 26 Number 3 May 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
