Eye (1987) 1,311-317

Management of the Macula

E. L. CHUANG Miami, Florida

Summary Age-related (AMD) is responsible for the majority of registered blindness in the elderly. photocoagulation can be offered as a treatment of proven value to only a proportion of patients with neovascular AMD. Clinically, our expectations must be tempered by the high incidence of recurrent subretinal vessels, the anatomic limitations of treatable lesions and the large number of ageing eyes for which there is no place for laser. In addition to improve­ ments in education, referral habits and the application of laser therapy which may have an impact upon visual loss due to AMD, there are promising directions to be explored in alternative modes of treatment and prevention.

It is well recognised that the leading cause of laser treatment, completed and in progress, blindness in the elderly is AMD. 1,2 This and and also cover limitations and failures of alternative designations such as senile macu­ therapy. Those manifestations of macular lar degeneration (SMD) are used by many ageing for which no treatment is currently authors to refer to all forms of macular ageing, appropriate will also be considered. Finally, whereas only those changes associated with mention will be made of less conventional loss of function are included under the desig­ therapeutic approaches under study and on nation AMD by others. The former definition the ultimate management, that is, possible is used here for drusen, retinal epi­ prevention. thelial detachment, geographic and subretinal (choroidal) neovascularisation, State of The Art-Laser Treatment manifestations of ageing which do not occur It is appropriate to begin discussion of laser sequentially but rather exist in an interrelated treatment by reviewing briefly the effects of manner. photocoagulation in the target and neighbour­ Only a small proportion of patients with ing tissues. 4 These are based upon the con­ age-related changes suffer significant visual version of light energy to heat, the effects of loss. 2 Though it is one of the least common which are determined by irradiance, absorp­ manifestations of the ageing macula, subreti­ tion and tissue pathlength. Factors such as nal neovascularisation (SRNV) or disciform power, duration and spot size comprise irra­ degeneration is responsible for the vast diance, while heat absorption depends upon majority of these blind eyes. 3 the wavelength employed relative to A significant proportion of these eyes pass present in the tissues and is affected by heat through a stage in which laser therapy can conduction as well as by light absorption and improve the visual prognosis. This review will scatter due to the lens. In the target tissues, concentrate upon neovascular complications the main heat-absorbing substances are of AMD, outlining the relevant studies of , xanthophyll and haemoglobin, each

Correspondence to: E. L. Chuang, Bascom Palmer Eye Institute, PO Box 016880, Miami, Florida 33101. From Retinal Diagnostic Department, Moorfields Eye Hospital, London, 312 E. L. CHUANG of which has a characteristic location lengths which must also be taken into account (pathlength) and relative absorption of dif­ in considering the effects of laser. ferent wavelengths. The clinically available include Argon Blue-green and Green Present Clinical Management of AMD only, Krypton Red and Yellow, and most Photocoagulation is the only effective recently, the tuneable Dye Laser with which a modality presently available for the treatment wavelength may be chosen to best suit the of any of the sight-threatening complications of AMD, and is correctly applied only to neo­ individual setting.5 vascular lesions. Our currently accepted Melanin has a broad spectrum of absorp­ approach is based upon the results of three tion, such that its relative concentration in the recent randomised clinical trials which have retinal pigment epithelium (RPE) and shown significantly improved outcome with choroid is the primary determinant of energy Argon Blue-Green laser treatment for extra­ absorption. Spread of heat to neovascular foveal membranes in elderly populations.7 -9 complexes adjacent to the RPE and originat­ These studies varied in specific criteria used ing from the choroid is the principal means by for patient selection, treatment or follow-up, which closure of SRNV occurs. Melanin con­ but many features were common to all three. centration varies considerably with race and Eligible membranes causing symptoms were age: as the concentration of melanin treated with heavy and confluent burns decreases with age, higher power levels are extending beyond the angiographic limits of needed in order to create the desired photo­ the lesion. Visual results were better in eyes coagulative effects. Melanin absorbs longer treated compared to those observed in all wavelengths less than shorter ones. Therefore three studies. In the Macular Photocoagula­ with Red, more energy penetrates the RPE to tion Study (MPS), visual loss of six or more reach the choroid, a partial explanation for lines of acuity was present in 60 per cent of the deeper burns characteristic of Krypton untreated eyes vs 25 per cent of treated eyes Red versus Argon Blue-Green. 18 months after treatment.7 Stable or Haemoglobin absorbs Blue, Green and improved vision was twice as likely in treated Yellow well, but longer wavelengths poorly. eyes at six months. Similarly, in the British Therefore, retinal vascular and secondary and French studies, all analyses favoured inner retinal damage can be minimised by the treatment over observation.8,9 use of Red, as has been demonstrated histo­ Unfortunately, obtaining and maintaining logically.6 Furthermore, if there is a thin layer the benefits of treatment goes far beyond the of blood associated with a neovascular mem­ technical application of laser. Persistent or brane, relatively better penetration is recurrent SRNV following laser is an all too afforded by Red wavelengths, delivering frequent event. All three randomised studies more energy to the deeper target tissues. as well as other retrospective analyses which Xanthophyll absorbs Blue most, Green have included Krypton Red-treated eyes have minimally and Yellow or Red least. Like identified open vessels in close to 60 per cent melanin, its concentration is partially deter­ of eyes after intended obliterative photo­ mined by race. Furthermore, as melanin con­ coagulation.10--13 The vast majority of these centration decreases with age, the use of arise from the site of the original neo­ increasing power levels in order to create an vascularisation and its treatment, with only 8 adequate burn potentially leads to more sig­ per cent of 'recurrent' membranes in treated nificant absorption by xanthophyll. The pres­ MPS eyes located independently from treat­ ence of xanthophyll in the central macula, ment scars. Virtually all the recurrences arise primarily in the outer plexiform layer means from the foveal treatment edge, underlining that damage to the neurosensory retina can be the well-recognised tendency of neovascular minimised in this location by the use of longer membranes to grow toward the foveola and wavelengths. With ageing, the lens contains perhaps modified laser absorption in this increasing amounts of xanthophyll, leading to location as well as reluctance to apply Blue­ greater absorption and scatter of short wave- Green laser close to xanthophyll pigment. MANAGEMENT OF THE AGEING MACULA 313

The majority appear relatively early: with nised that the biologic behaviour of NVMs almost five year follow-up in the MPS, over 70 includes an initial period of greatest activity per cent of recorded recurrences were identi­ and growth. 18 Experience has identified an fied within the first year. 10 It is of significance interval of weeks from the onset of symptoms that analysis to date has not identified specific beyond which laser therapy results in a poorer features other than distance from the foveal visual outcome. 19 After treatment, patients avascular zone, which might be useful predic­ should be clearly and repeatedly informed of tors of eyes at higher risk for recurrence in the means and need to monitor central vision Argon treated eyes. The long-term visual out­ and of the importance of seeking immediate come is worsened because of the high number attention should symptoms arise. They and of recurrences, but still remains better than no referring eye care specialists must also have treatment at all since laser can be reapplied in ready access to appropriate evaluation. These eyes with recurrent SRNV which continue to measures should enhance our ability to meet treatment criteria. 14 approach the highest possible success rate The nature of recurrences reflects not only afforded by photocoagulation. features of the biologic nature of SRNV but In the best of circumstances, there will also less than optimal aspects of our presently always be individuals in whom the location of accepted treatment approach. If we can better an active NVM will begin or become sub­ understand and manage this common sequel foveal, so that there can be no hope for to laser treatment in neovascular AMD, the normal central vision. In such instances, laser visual prognosis in macular ageing will may still improve final visual function. It has undoubtedly improve. Though the use of been proposed that the size of the ultimate Argon Blue-Green is the only modality pres­ scotoma can be limited by photocoagulation ently supported by results of randomised of subfoveal SRNV. 20 Patients learn to use studies, there is ample theoretical and mount­ neighbouring photoreceptors after loss of the ing clinical experience to indicate that other fovea. 21 Also, there is evidence that patients wavelengths may be more suitable in many with smaller scotomas have better functional circumstances. 4,15-I7. The choice of wave­ vision, at least for some tasks. 22 This contro­ length should be directed by the principles versial technique would necessarily include outlined above applied to variations in mem­ intentional destruction of surrounding func­ brane location, background fundus pigmenta­ tioning retina to obliterate effectively choroi­ tion, the amount of xanthophyll pigment, or dal neovascularisation. A randomised trial is the presence of subretinal fluid, blood or reac­ being organised as an extension of the MPS to tive pigment. For example, in instances in assess the value of subfoveal treatment, but which there is little melanin present in either such therapy is not recommended at present. the RPE or choroid, Argon Green with higher absorption by haemoglobin and melanin may Manifestations of AMD not Appropriate for be a more appropriate choice. The use of Red, Photocoagulation Green, or Yellow may allow both treatment Three other manifestations of ageing of the of membranes closer to fixation and more macula are presently unsuitable for treat­ adequate obliteration on the foveal side of the ment. SRNV may be strongly suspected, but lesion. Prospective trials of Krypton Red and not defineable angiographically, producing Argon Green for SRNV less than 200 microns poorly circumscribed yet progressive hyper­ from, but not beneath the foveola are well fluorescence. Such an appearance may underway in the United Kingdom and in the accompany a distinct membrane as a flat rim United States of America in hopes of answer­ of hyperfluorescence which only in retrospect ing this question. has gradually and quietly enlarged. A recent Beyond more effective treatment of study suggests that eyes with such 'occult' primary or recurrent SRNV, steps other than membranes maintain better vision under laser can be taken to improve visual outcome observation than with photocoagulation. 23 On when disciform degeneration occurs. The tim­ the one hand, their often benign behaviour is ing of evaluation is critical since it is recog- quite compatible with prolonged good acuity, 314 E. L. CHUANG while on the other, there is significant risk of Second Eyes and Drusen Alone incomplete treatment with a high probability The next concern of both the patient and the of accelerated activity. ophthalmologist is the other eye. For indivi­ Retinal pigment epithelial detachments duals with disciform degeneration in one eye, (RPED) as a manifestation of AMD are con­ the risk of developing SRNV in the second eye 12-15 . sidered exudative by some authors, implying lies in the range of per cent per year.32 33 the presence of SRNV. On the contrary, Relatively greater risk may exist for eyes with many, large or highly confluent drusen. RPEDs are not necessarily associated with What about individuals with drusen alone new vessels.24-27. They may remain stable with in each eye? There are no prophylactic quite good vision or even resolve spon­ measures by which the risk of neovascular taneously. SRNV becomes apparent in complications can be reduced nor are there approximately one-third of what begin as means of preventing the mild loss of vision serous RPEDs, more commonly in those which may accompany drusen itself. The epi­ which tend to be central, large, associated demiologic evidence implies that of the vast with serous retinal detachment, and numbers of elderly individuals manifesting angiographically late filling and irregularly these age-related changes in Bruch's mem­ . fluorescent.2 6 27 Even so, retinal function may brane, only a small number are destined to be relatively good over vascularised RPEDs develop SRNY. The actual risk is difficult to since the anatomic arrangement of vascular determine but cumulatively is probably in the supply (choroid-derived new vessels), RPE neighbourhood of 12 per cent over five and photoreceptors may be preserved. The years.34 Characteristics which may indicate a visual prognosis for RPEDs is therefore cer­ higher risk for the development of SRNV tainly not uniformly poor. In a prospective, include a family history of disciform degener­ randomised trial, visual outcome was statis­ ation and the presence of significant con­ tically worsened by laser treatment of fluence of drusen or focal hyper­ RPED.28 In some instances, neovascular pigmentation.29.34 vessels previously contained beneath the RPE As more effectivemethods of treatment are may have been stimulated and allowed to pen­ developed, it becomes increasingly relevant etrate into the subretinal space. In others, to address the issue of how best to screen for photocoagulation induced tears of the RPE. treatable disciforms. Should all patients with Since it can initiate or accelerate deterioration drusen be appraised of the possibility of in a condition with a variable prognosis, laser SRNV, the symptoms and what steps should is not recommended to all RPEDs. Whether a be taken? Such a policy and the number of subset of these lesions may fare better with resultant examinations would have an enor­ photocoagulation remains to be determined, mous impact upon the eye-care services. In although such a group was not identifiedin the this regard, there is hope for the development previous study.28 of low cost methods of screening and further Well-circumscribed atrophy of the outer identification of predictors of eyes at highest retina may appear as a late manifestation of risk. AMD.29,30 This has been referred to as geo­ graphic or areolar atrophy. Though histologic evidence of choroidal neovascularisation Low Vision Aids often coexists with atrophic changes, 3l it is For those in whom no further therapy is poss­ uncommon clinically to find concurrent or ible, low vision clinics play an important role subsequent disciform degeneration in eyes in assessing and utilising remaining visual with geographic atrophy.29 Long after either function. The practical limit appears to be active SRNV or after a tear of the RPE, an vision of fingercounting at approximately one appearance may evolve which clinically simul­ metre. This of course depends as much upon ates primary atrophy. Laser photocoagulation the adaptability, physical status and motiva­ is not appropriate for any of these atrophic tion of the patient as upon the macular lesion forms of AMD. itself. Perhaps 70 per cent of those referred MANAGEMENT OF THE AGEING MACULA 315 can be helped substantially by these includes the action of light-induced, oxygen­ techniques. 35 derived free radicals on polyunsaturated fatty acids, components of all cell membranes. Other Approaches Metabolic systems controlling or limiting Several lines of research suggest alternative peroxidation can be modified by a number of approaches which may be useful against natural antioxidants in the retina such as SRNV beside obliterative laser treatment. superoxide dismutase, ascorbate, melanin, Normal Bruch's membrane is an avascular taurine and vitamin EY Animal models have structure, the barrier function of which breaks been established in order to manipulate die­ down with age. 36 There is considerable evi­ tary composition, vitamin supplementation or dence for the role of cellular mediators such as deletion, and light exposure in order to gain macrophages in the production of SRNV. 37,38 insight into as well as to identify Vasoactive factors operating between RPE points at which intervention may be and choroidal vessels have been postulated attempted. 48.49 1t may someday be possible to which may also be important in the genesis of benefit in man from the control of dietary choroidal neovascularisation. 39 Agents such , ocular protection from potentially haz­ as corticosteroids or growth suppressants ardous wavelengths or alteration of age­ might be used to manipulate cellular com­ related loss of melanin from the RPE. What­ ponents or the presumed angiogenic stimulus ever the results of such investigations, from for SRNY. 40 There may however be what we know of the progressive nature and undesireable effects upon RPE, inflammatory early onset of ageing changes, such measures and other cells which participate in repair would have to be initiated virtually in child­ and/or limit neovascular growth.41.42 hood in order to be useful. A great deal has been learned from cell In summary, we are faced with quite vari­ culture, especially of RPE cells, now an estab­ able consequences of ageing in the macula, lished research tool in vision research. Vari­ only one of which, sub retinal neovascularisa­ ous factors have been identifiedby which intra tion can currently be approached with treat­ and intercellular metabolic systems can be ment of proven benefit. Even with laser modified. 43,44 Injection of cultured RPE cells treatment, a discouragingly small proportion beneath the retina is under investigation45 and of affected eyes can be successfully treated. studies are in progress on the transplantation However, advances in photocoagulation tech­ of retinal tissues. 46 In the future, it may not be niques and continuing research will hopefully totally unrealistic to envision cell repopula­ improve prospects for the future management tion in some settings of AMD. of the ageing macula.

Prevention? The author is grateful to Professor A. C. Bird for Thus far, available and promising therapeutic review of the manuscript. approaches have been discussed which can be applied to eyes after they have developed References I advanced ageing changes. Instead, can Sorsby A: The incidence and causes of blindness in England and Wales 1948-1962. Reports on measures be taken which modify or even pre­ Public Health and Medical Subjects (No. 114). vent the vision-threatening alterations which London. HMSO, 1966; 11-14. occur with ageing? 2 Leibowitz HM, Krueger DE, Maunder LR, et al: Studies of changes in the cellular micro­ The Framingham Eye Study Monograph; an ophthalmological and epidemiological study of environment of the retina with age show that cataract, glaucoma, diabetic retinopathy, macu­ there is clearly a link between continuous lar degeneration and visual acuity in a general photoreceptor outer segment turnover, disc population of 2631 adults, 1973-1975. Surv. phagocytosis, accumulation of lipofuscin, and Ophthalmol. 1980, 24 (Suppl): 428-71. changes in Bruch's membrane which lead to 3 Hyman LG: Senile macular degeneration: an epi­ demiologic case control study, Thesis, the Johns the clinical manifestations of AMD. As out­ Hopkins University, Baltimore, 1981. lined by Feeney-Burns,47 lipofuscin formation 4 Mainster MA: Wavelength selection in macular proceeds through a complex process which photocoagulation: tissue optics, thermal effects, 316 E. L. CHUANG

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