Continuing education CET Age-related macular disease Part 2 – Detection of wet AMD

In the second part of this series, Dr Frank Eperjesi looks at the clinical evaluation of suspect maculopathy with particular emphasis on the early detection of the wet form. C7881, one general CET point, suitable for optometrists and DOs

he first article in this three- part series (Optician, October 19) looked at the classifica- tion of AMD and described the clinical features of dry T AMD as: discrete yellow spots at the macula (drusen), hyperpigmentation of the RPE, sharply demarcated areas of RPE depigmentation (hypopigmenta- tion) with focal hyperpigmentation of the RPE a high-risk feature for subse- quent wet AMD development. The clinical features of wet AMD were described as geographic atrophy of the RPE with visible underlying choroidal Figure 1 Dry AMD Figure 2 Wet AMD vessels, pigment epithelial detachment (PED) with or without neurosensory and halt vision loss or even reverse vision onset of the inevitable and progressive detachment, subretinal or sub-RPE loss with smaller and less central lesions. significant visual loss associated with neovascularisation, fibroglial scar tissue, According to recent studies investigating the condition. haemorrhage and exudates. the outcome of these treatment modali- While dry AMD is a slowly progres- ties, the larger the lesion at baseline the Using symptoms to detect wet sive disease with vision loss taking place smaller the treatment benefit in terms of AMD over many years, wet AMD is a much the absolute level of visual acuity at two Detection of wet AMD often involves more rapidly progressive disease and years after the initiation of treatment. instructing patients to report symptoms is the main cause of catastrophic and The natural history of CNV is that such as distorted lines, blurriness, permanent vision loss, which can occur it gradually increases in size by an reduced vision and dark areas in their over a matter of a few days. It is estimated average of 10 to 18µm daily2 and that visual field or use of the Amsler grid that 18 per cent of patients with inter- it grows closer to the foveal centre in and being alert to new symptoms of mediate AMD (many medium-sized about 50 per cent of cases.3 Therefore, metamorphopsia, visual field scotoma drusen >63µm but <125µm or one large early detection of AMD-related lesions and blurred vision or micropsia. Many drusen >125µm – the central retinal is crucial in the management of these investigators have pointed out that the vein is about 125µm in diameter at the patients. Reeves4 estimates that in her patients who notice these symptoms optic nerve head) in at least one eye and experience the transition to early wet or changes in the Amsler grid are 43 per cent of patients with advanced AMD is not recognised soon enough in detected relatively late in the stage of AMD in one eye only develop choroi- approximately 15 per cent of patients. the disease when a large scotoma is dal neovascularisation (CNV), in other By the time an ophthalmologist sees already present.8,9 words wet AMD, within five years.1 these patients they have severe, irrevers- Wet AMD accounts for only 10 per ible vision loss for which treatment has Change in refractive error cent of all AMD but accounts for 95 minimal impact. She goes onto state that In the author’s experience it is worth per cent of serious vision loss. This takes ‘ideally, diagnosis and treatment should further investigating older patients the form of a localised loss of vision occur right after conversion to wet (especially those with more than one (scotoma) and or distortion of vision AMD before vision loss has occurred’. risk factor for AMD – see article three (metamorphopsia). This article will Recent publications have emphasised in this series) who present with a reduc- review techniques that can be used in the benefits of treating AMD lesions tion in myopia or an increase in hyper- primary care optometric setting in the while they are still relatively small.5,6 opia (hyperopic shift), particularly for timely detection of wet AMD. Loewenstein7 reported a case where a those without cortical lens opacities patient with a small extrafoveal lesion (these have been reported to cause this Early detection of wet AMD and visual acuity of 6/12 presented two type of refractive error change). Research has shown that the major current months later with 6/36 and an extensive A hyperopic shift without cortical lens techniques used in the treatment of wet subfoveal CNV without treatment. opacities could be due to type 2 diabetes AMD (anti-VEGF and photodynamic This reflects the importance of identi- (however, this most commonly causes a therapy) are more likely to be successful fying the presence of CNV before the myopic shift) or due to CNV elevation

36 | Optician | 16.11.07 opticianonline.net CET Continuing education

of RPE or neurosensory retina. Further were evaluated the detection rate was investigation could involve slit-lamp even lower.11 indirect binocular ophthalmoscopy, There are several reasons for the poor referral for an ophthalmological opinion performance of the Amsler grid: or both. Elevation due to a subtle hyper- ● Awareness of visual field defects opic shift such as 0.75DS may result in is limited, with the patient not being retinal elevation that is too subtle to cognisant of any defect until the detect using slit-lamp indirect binocu- scotoma is considerably large and lar ophthalmoscopy, so it is useful to ask already includes central vision because the patient if they have experienced any of foveal involvement of the lesion. metamorphopsia or micropsia to help This can be partly explained by cortical with the differential diagnosis. completion or the ‘filling in’ phenome- non.16 The correlation relation between Ophthalmoscopy scotoma size and detection rate has been Certain types of wet AMD are very demonstrated.11 easy to detect even when using a direct Figure 3 Forsee PHP from Notal Vision ● The inability to properly maintain ophthalmoscope through an undilated fixation during testing pupil (Figure 1 dry AMD and Figure 2 a screen-based Amsler grid is reduced ● The crowding effect caused by the wet AMD). Early CNV changes may progressively and just before the target multiple lines that are peripherally not be detectable using a monocular disappears altogether relative scotomata presented in the Amsler grid causing technique and it would be good practice become apparent to the patient. With low sensitivity of the test and adding to investigate patients presenting with the standard and threshold Amsler to its poor performance symptoms of distorted lines, blurriness, tests mydriasis and ophthalmoscopy ● The non-interactive nature of the reduced vision, dark areas in their visual should be avoided immediately prior to Amsler grid, rendering it unsuitable field, metamorphopsia or micropsia using the Amsler grid especially with for monitoring patients because factors with slit-lamp-based binocular indirect suspected AMD.10 Neither the standard such as quality of examination perform- ophthalmoscopy. However, slit-lamp nor threshold versions are as good as ance and reliability measures, such as indirect biomicroscopy’s clinical utility conventional perimetry when it comes false positives and false negatives is variable and depends to a great extent to detecting scotomata less than 6º (the cannot be assessed upon the expertise of the examiner and average optic nerve head is 7º) in diame- ● Low compliance to perform the lesions may still be missed. ter.11 It seems common practice for eye Amsler grid at home. care professionals to supply patients Using the Amsler grid to detect with a copy of the recording sheet Preferential hyperacuity wet AMD (black grid on a white background) for perimeter As the early detection of wet AMD is home testing. This may result in spuri- To try to address some of the shortcom- crucial, patients at risk are encouraged ous results as bright backgrounds with ings of the Amsler grid a new method to perform self-monitoring, often using black detail have been shown to result in using the hyperacuity function has been an Amsler grid. The Amsler grid can anomalous illusions of shape and colour developed. This was initially named the be used to detect scotomata (missing akin to the pattern glare described by ‘Macular Computerised Psychophysical or blurred lines) and metamorphopsia Wilkins and colleagues in their work Test’ and described by Loewenstein and (bowed or distorted lines) and the likely on reading problems.12 It would be colleagues in 200317 but has become position of the associated lesion. The better to guide patients or carers to known as the ‘Preferential Hyperacuity basic grid (Amsler chart 1) is printed an appropriate website from which Perimeter’ (PHP). The test was origi- in white on a dull black background. they can print a white grid on black nally marketed by Zeiss as the ‘Preview It is intended for use at 30cm (with the background version for themselves or PHP’ and is now available from Notal patient fully corrected for that distance) use a screen-based grid for self-testing. Vision (www.notalvision.com) as the when each square subtends an angle of Unfortunately, Franklin10 and others13 Forsee PHP (Figure 3). In this second- 1º and the whole chart 20º. Amsler have reported that compliance with generation format it has a number of chart 2 has guidelines to help those self-testing is low. The most common improvements over its first incarnation patients who already have a central presenting symptom of wet AMD is in terms of improved speed and ease of scotoma to estimate where the central blurred vision and distortion when interpretation. This system was origi- fixation is located. The original test was reading, rather than changes on the nally developed to evaluate the central intended for use under normal reading Amsler chart even in patients who are macular visual field and potentially illumination conditions. A variation supposed to be self-monitoring.14 provide early detection of wet AMD. It of the standard test is the threshold The Amsler grid has been shown to generates a non-invasive eye exam that Amsler test in which the task light- be an unreliable tool for diagnosing allows the detection of elevations in the ing is reduced by dimming the local central visual field defects in patients RPE and the bowing of the photorecep- illumination or by introducing filters with AMD.9,15 Although the threshold tor layer – both consistent with conver- such as those used with the Titmus Amsler grid has been reported to show sion from intermediate to an advanced stereoacuity test or the Mallet unit.9 a better performance, 50 per cent of stage or wet AMD. Hyperacuity also Some reports have suggested that this all scotomata in the macular region termed vernier acuity is defined as the makes the Amsler grid more sensitive still remain undetected by either one. ability to perceive a difference in the to detecting small, recently developed This means that one out of every two relative spatial localisation of two or CNV lesions that cause relative but cases of wet AMD could be missed if more visual stimuli. Hyperacuity thresh- not absolute scotomata.9 Franklin10 has the eye care professional were to rely old may be as low as 3 to 6 seconds of also promoted the use of a computer- solely on the Amsler grid for detection. arc18 – in other words it is about 10 times based test in which the luminance of Moreover, when scotomata of 6º or less more sensitive than standard visual opticianonline.net 16.11.07 | Optician | 37 Continuing education CET

acuity.19 Through its use of hyperacu- on these responses a visual field map ity, the Forsee PHP can overcome the is constructed, analysed and compared brain’s ability to compensate for small to normative data, thereby determin- defects and may identify CNV lesions ing the likelihood of this defect being prior to the patient experiencing any Figure 4 Patient is shown a dotted line with some dots CNV (Figure 7). The fast flash time and significant visual loss. Hyperacuity deviating from the line (artificial distortion). The artificial use of hyperacuity allow the device to stimuli are highly resistant to retinal elevation is made progressively smaller overcome brain compensation mecha- image degradation and are suitable for nisms to better capture visual defects. assessing retinal function in patients The PHP has been shown to detect with lens opacities.19 Furthermore, recent onset CNV with high sensitiv- there is no decrease in hyperacuity with ity (82 per cent) and differentiate these age between 20 and 85 years.20 Patients patients from those with intermediate must have better that 6/60 to be able to AMD with high specificity (88 per perform the test. cent). PHP was also shown to be more The patient places their head on a chin sensitivite than slit-lamp indirect binoc- rest and views the monitor with one ular biomicroscopy.21 The same group eye occluded. Task-orientated fixation has shown that the PHP had a greater was incorporated to try to eliminate positive predictive value and sensitiv- the need for continuous fixation of a ity compared with the Amsler grid for central located target. This means that detecting wet AMD-related lesions. Of the patient can move their eye to fix Figure 5 The patient use a stylus pen to touch the screen 32 patients with CNV, 30 (94 per cent) the stimulus without the results being where the distortion was located were detected by the PHP and only 11 affected, which is unlike the majority (34 per cent) with the Amsler grid.17 of visual field analysers, were central Previous tests can be retrieved from and maintained fixation is paramount memory and therefore long-term track- to the successful application of the test. ing of retinal changes is easily achiev- The patient is presented with a pattern able. In the US, the PHP has FDA of dotted lines projected for 160msec to approval for monitoring the progres- the central 14º of the visual field (Figure Figure 6 Competition occurs in the presence of a CNV. When the sion of AMD and detecting the conver- 4). Each line contains an artificial distor- CNV causes a larger elevation than the artificial one, the sion of dry to wet AMD signalled by the tion at a different magnitude and the patient will pick the spot of true distortion onset of CNV. distortion serves as a competitive stimu- Reeves4 has advocated that all AMD lus to any retinal disease-related distor- patients should have a baseline PHP. tion (hyperacuity defect) that might Then, depending on the absence or appear on the presented pattern. The presence of high-risk features for patient uses a stylus pen to touch the CNV, repeat testing may be performed screen where the distortion was located anywhere from two to four times a year. (Figure 5). When there is a CNV lesion, Interestingly, Reeves4 has suggested that attention competition between the artifi- PHP in conjunction with OCT may cial distortion and the pathologic distor- also help minimise the use of angiog- tion takes place in the patient’s brain. raphy (not without its risks) during In general, the brain ignores the smaller follow up. of two stimuli and this phenomenon is exploited in PHP testing to assess the Conclusion magnitude of the retinal disturbance It is important for eye care profession- (Figure 6). Varying sizes of artificial als to be aware that the Amsler grid distortion are presented, allowing a will only detect half of those patients quantification of the retinal distortion by with early wet AMD and before new analysing the patient’s response. Based Figure 7 Test results from the Forsee PHP techniques such as the PHP become

What did your patients wear to bed last night?

Many patients sleep in their lenses1, whether or not this is the recommended wearing schedule. By fitting AIR OPTIX® NIGHT&DAY® you can ensure that your patients are wearing the most breathable soft lens available. These lenses can be worn continuously for up to 30 nights and days – wherever those 30 nights and days might be2. This means you can sleep easier at night as well.

1. CIBA Vision. Data on file, 2006. 2. CIBA Vision. Data on file, 2006. © CIBA Vision (UK) Ltd, a Novartis Company, 2007.AO 07 04

38 HFK009| Optician OSNight_StripADNew.indd | 16.11.07 1 opticianonline.net9/11/07 09:58:53 Continuing education CET

more widely available it is important to annual meeting. Retina, 2007;27:873-8. Ophthalmol, 1995;120:322-9. use a combination of patient symptoms 8 Achard OA, Safran AB, Duret FC, Ragama 17 Loewenstein A, Malach R, Goldstein M, (especially blurred, missing or distorted E. Role of the completion phenomenon in Leibovitch I, Barak A, Baruch E, Alster Y, lines), reduced distance and near visual the evaluation of Amsler grid results. Am J Rafaeli O, Avni I, Yassur Y. Replacing acuity, hyperopic shift and slit-lamp Ophthalmol, 1995;120:322-9. the Amsler grid: a new method for indirect binocular microscopy to detect 9 Wall M, Sadun AA. Threshold Amsler grid monitoring patients with age-related the presence of new CNV. The newly testing. Cross-polarising lenses enhance macular degeneration. Ophthalmology, emerging treatment options for wet yield. Arch Ophthalmol, 1986;104:520-3. 2003;110:966-70. AMD and in particular anti-VEGF thera- 10 Franklin A. The Amsler charts. Optician 18 Westheimer G. The spatial sense of the pies have made it incumbent on eye care February 8, 2002, No 5837, 223:22-24. eye. Proctor lecture. Invest Ophthalmol Vis professionals to upgrade monitoring 11 Schuchard RA. Validity and interpretation Sci, 1979;18:893-912. techniques for earliest possible detec- of Amsler grid reports. Arch Ophthalmol, 19 Enoch JM, Williams RA, Essock EA, tion of CNV. The use of PHP has been 1993;111:776-80. Barricks M. Hyperacuity perimetry. shown to be more accurate than slit- 12 Wilkins AJ, Nimmo-Smith I, Jansons JE. Assessment of macular function through lamp indirect binocular biomicroscopy Colourimeter for the intuitive manipulation ocular opacities. Arch Ophthalmol, and twice as accurate as the Amsler grid of hue and saturation and its role in the 1984;102:1164-8. and could significantly enhance the rate study of perceptual distortion. Ophthalmic 20 Lakshminarayanan V, Aziz S, Enoch JM. of early detection of CNV development Physiol Opt, 1992;12:381-5. Variation of the hyperacuity gap function leading to earlier treatment and better 13 Fine AM, Elman MJ, Ebert JE, Prestia PA, with age. Optom Vis Sci. 1992;69:423-6. final visual acuity. The use of PHP for Starr JS, Fine SL. Earliest symptoms caused 21 Alster Y, Bressler NM, Bressler SB, home monitoring is currently being by neovascular membranes in the macula. Brimacombe JA, Crompton RM, Duh YJ, Gabel investigated by its developers. ● Arch Ophthalmol, 1986;104:513-4. VP, Heier JS, Ip MS, Loewenstein A, Packo 14 Fine SL. Early detection of extrafoveal KH, Stur M, Toaff T; Preferential Hyperacuity ● The author has no commercial inter- neovascular membranes by daily central field Perimetry Research Group. Preferential est in any of the equipment described. evaluation. Ophthalmology, 1985;92:603-9. Hyperacuity Perimeter (PreView PHP) for 15 Roy MS. Vision loss without Amsler detecting choroidal neovascularisation References grid abnormalities in macular subretinal study. Ophthalmology, 2005;112:1758-65. 1 Age-Related Eye Disease Study Research neovascularisation. Ophthalmologica, Group. A randomised, placebo-controlled, 1985;191:215-7. ● Dr Frank Eperjesi is director of the clinical trial of high-dose supplementation 16 Achard OA, Safran AB, Duret FC, Ragama optometry undergraduate programme at with vitamins C and E, beta carotene, and E. Role of the completion phenomenon in the School of Life and Health Sciences at zinc for age-related macular degeneration the evaluation of Amsler grid results. Am J Aston University and vision loss: AREDS report no. 8. Arch Ophthalmol, 2001;119:1417-36. 2 Macular Photocoagulation Study Multiple-choice questions – take part at opticianonline.net Group. Argon laser photocoagulation for neovascular maculopathy. Five-year What percentage of patients with Hyperacuity has a resolution of results from randomised clinical trials. Arch 1intermediate AMD will develop a CNV 4approximately which of the following? Ophthalmol, 1991;109:1109-14. after five years? A 6º 3 Laser photocoagulation for juxtafoveal A 10 B 7º choroidal neovascularization. Five-year B 15 C 125µm results from randomised clinical trials. C 18 D 5 secs of arc Macular Photocoagulation Study Group. Arch D 20 Ophthalmol, 1994;112:500-9. The Forsee PHP analyses which of the 4 Reeves D. Early detection and better The standard Amsler grid cannot detect 5following? results for AMD. Retina Today, 2007;July/ 2lesions smaller than which of the A 7º around the fovea August:1-2. following? B 14º around the optic nerve head 5 Gonzales CR; VEGF Inhibition Study in A 64µm C At the level of the internal limiting membrane Ocular Neovascularisation (V.I.S.I.O.N.) B 125µm D. 3 to 6 seconds of arc around the fovea Clinical Trial Group. Enhanced efficacy C 14º of arc associated with early treatment of D 6º of arc Which one of the following is correct? neovascular age-related macular degeneration 6 with pegaptanib sodium: an exploratory The threshold Amsler test involves which A Compared to the Amsler grid the PHP is about analysis. Retina, 2005;25:815-27. 3of the following? eight times better at detecting CNV lesions 6 Michels S, Wachtlin J, Gamulescu MA, A Preferential hyperacuity perimetry B The Amsler grid will detect about 80 per cent Heimann H, Prunte C, Inhoffen W, Krebs B Standard Amsler testing and reduced of cases with early CNV I, Schmidt-Erfurth U. Comparison of early illumination C Slit lamp indirect binocular microscopy is retreatment with the standard regimen C Carrying out standard Amsler testing better at detecting early CNV than PHP in verteporfin therapy of neovascular immediately after direct ophthalmoscopy D The PHP can provide information on levels of age-related macular degeneration. D Standard Amsler testing and very high levels hyperopic shift in dioptres Ophthalmology, 2005;112:2070-5. Epub of illumination 2005 Oct 12. 7 Loewenstein A; Richard & Hinda To take part in this module go to opticianonline.net and click on the Continuing Education Rosenthal Foundation. The significance section. Successful participation in each module of this series counts as one credit towards of early detection of age-related macular the GOC CET scheme administered by Vantage and one towards the Association of degeneration: Richard & Hinda Rosenthal Optometrists Ireland’s scheme. The deadline for responses is December 13 Foundation lecture, The Macula Society 29th ●

40 | Optician | 16.11.07 opticianonline.net