Ординатура / Офтальмология / Английские материалы / Age-Related Changes of the Human Eye_Cavallotti, Cerulli_2008

Drusen. In this case, the atrophy typically begins around the perimeter of the fovea in a band of microreticular hyperpigmentation.

Stages of Non-Exudative AMD

Different grading schemes have been used in various studies for both non-exudative and exudative AMD. All of these have limitations, though, and can be misleading. By describing varying degrees of AMD in stages, these studies imply that earlier stages of AMD inexorably progress to more advanced stages. This is not true. In fact, many patients who possess only Drusen continue with a stable ophthalmic exam for the rest of their lives. However, the presence of Drusen does represent a risk for the development of visual loss and neovascular AMD, particularly if the Drusen are large and numerous.4

In general, early non-exudative AMD is defined as the presence of several medium-sized Drusen with either RPE hyperor hypopigmentation. Patients usually have no visual complaints (see Fig. 16.1).

Intermediate non-exudative AMD consists of numerous medium and/or large Drusen. Visual acuity is typically normal, and these patients may be asymptomatic, although they commonly complain of nyctalopia (see Fig. 16.2).

Advanced non-exudative AMD is defined as geographic atrophy. As long as the area of geographic atrophy does not involve the fovea, visual acuity generally remains normal, although patients may complain of nyctalopia or difficulty reading a line of print. Once geographic atrophy involves fixation, visual acuity typically drops to 20/200 or worse (Fig. 16.3).

Fig. 16.1 Category 1 – Few or No Drusen

a prophylactic benefit. In addition, if Drusen were prominent in the fovea, such a reduction might also have therapeutic implications and allow visual improvement. This rational was the impetus for several of the studies discussed below.

Age-Related Eye Disease Study (AREDS)6

This pivotal trial evaluated the effect of high-dose vitamins C and E, beta-carotene, and zinc supplements on the progression of AMD and visual acuity. Subjects were randomly assigned to receive daily tablets containing antioxidants (500 mg vitamin C, 400IU vitamin E, 15 mg beta carotene), 80 mg zinc oxide with 2 mg copper, antioxidants plus zinc, or placebos. Copper was added to prevent zinc-induced anemia. More than 4,000 subjects were involved and were followed for five years or more.

Subjects with high-risk non-exudative AMD—defined as extensive intermedi- ate-size Drusen, at least 1 large Drusen, noncentral geographic atrophy, or advanced AMD in at least one eye—benefited from supplementation with antioxidants plus zinc. Individuals in the group assigned to the combination supplement had a 25 percent reduction of risk for progression to advanced AMD, and a 19 percent risk reduction in the rate of moderate vision loss (≥ 3 lines of visual acuity) after five years. The AREDS trial substantiated the benefit of vitamin and mineral therapy in patients with non-exudative AMD.

Complications of Age-Related Macular Degeneration Prevention

Trial (CAPT)8

CAPT evaluated the effectiveness and safety of low-intensity grid treament with 532 nm argon laser in the prevention of visual acuity loss among participants with bilateral large Drusen. Participants were followed for five years.

After five years, there was no difference in visual acuity between treated and observed eyes (20.5% losing at least three lines in both groups). There also was no difference between groups for the development of choroidal neovascularization (13.3% in both groups).

Prophylactic Treatment of Age-Related Macular Degeneration (PTAMD)7

This study sought to determine whether a grid of mild subthreshold, 810 nm diode laser would have a prophylactic benefit on preventing non-exudative AMD from progressing to the neovascular form, and if laser treatment would improve the

long-term visual acuity compared with the natural history of the disease. The treatment regimen differed from the CNVPT and CAPT (see below) studies in two important ways. The first was that the laser applications were intentionally very mild, so that the spots could not be seen directly upon placement (subthreshold). (see Fig. 16.4.) The second was that no retreatments were allowed. The PTAMD study was divided into two arms—patients with multiple large Drusen in one eye and neovascular AMD in the other, and patients with multiple large Drusen in both eyes. Participants were followed for three years.

In the unilaterally eligible group, laser treatment placed the patients at higher risk of developing neovascular AMD than with observation alone (15.8% vs. 1.4% after 1 year), without significant difference in visual acuity loss.

In the bilaterally eligible group, diode laser treatment had no effect on the development of neovascular AMD (11% vs. 9%), and had a negligible effect on visual acuity (mean improvement of 1.5 letters compared to the observation group). A subset of patients whose vision was impaired at study entry did, however, have a modest benefit in visual acuity, greater than the mean of 1.5 letters.

Choroidal Neovascularization Prevention Trial (CNVPT)5

This study aimed to describe the short-term effects of low-intensity 532 nm argon laser treatment to eyes with Drusen that were at risk of developing choroidal neovascularization. The study consisted of two arms—the Bilateral Drusen Study and the Fellow Eye Study. The Bilateral Drusen Study included patients with non-exudative AMD with more than 10 medium or large Drusen in each eye. The Fellow Eye Study included patients with one eye as described above and one eye with exudative AMD. The treatment consisted of grid laser within the macula that spared the foveal avascular zone. Retreatment was applied whenever the area of Drusen had not been reduced by 50 percent or more. Subjects were followed for 18 months.

Fig. 16.4 PTAMD – Annular grid pattern of subthreshold laser

In both arms of the study, the area of Drusen decreased with laser treatment. Although the incidence of CNV was negligibly increased in the treatment group versus the observation group in the Bilateral Drusen Study (2.6% vs. 1.3%), the rate of CNV was higher in the Fellow Eye Study (16.9% vs. 3.3%). Visual acuity remained similar between both treatment and observation groups in the Bilateral Drusen Study, but was worse in the treatment group of the Fellow Eye Study.

Results from the Bilateral Drusen Study laid the foundation for the Complications of Age-Related Macular Degeneration Prevention Trial (CAPT), which will be described later.

Multi-center Investigation of Rheophoresis I (MIRA I)9

Rheophoresis, a form of double-filtered plasmaphoresis, is an extracorporeal blood filtration procedure, and an established method for reducing certain molecules in plasma. The rationale for its use for AMD is based on the potential to modify the diffusion through Bruch’s membrane, improve microcirculation, and change the complement cascade.

MIRA I failed to demonstrate a significant difference in visual acuity between a treatment and placebo group at 12 months. A gain of 0.8 lines was only demonstrated when post-hoc analysis removed any participants who had cataract surgery, cataract progression, laser capsulotomy, fewer than four rheophoresis treatments, or central geographic atrophy.

A proposal for an additional Phase III clinical trial has been submitted to the FDA, and this new trial is anticipated to be launched in 2007.

Age-related Eye Disease Study II (AREDS II)

AREDS II will evaluate supplements of macular xanthophylls (lutein and zeaxanthin) and omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid) on the development of neovascular AMD and geographic atrophy, and is currently enrolling participants. Although lutein is widely advocated as an eye supplement, it was unavailable in sufficient commercial quantities to be studied in AREDS I.

Conclusion

Non-exudative AMD is a multi-factorial disease that will undoubtedly be seen in increasing numbers as the world population continues to age. Non-exudative AMD includes a wide spectrum of macular changes, with a similarly wide spectrum of

Chapter 17

Treatment of Intraocular Pressure

in Elderly Patients

Monika Schveoller, MD, Iliana Iliu, MD, Nicola Pescosolido, MD, and Angelica Cerulli, MD

Abstract The aim of this paper is to study the effect of many systemic antihypertension drugs on intraocular pressure and on the visual field.

Six hundred patients were enrolled in this experiment with the approval of the Ethical Committee of our hospital. All patients were divided into four groups: the first group of 200 patients was treated with local or systemic administration of a calcium channel blocker; the second group of 200 patients was treated with oral or systemic administration of β-blockers; the third group of 100 patients was treated with systemic administration of ACE inhibitors; and the fourth group of 100 patients was treated with a diuretic drug (acetazolamide). All patients were subjected monthly to measurements of their systemic blood pressure, intraocular pressure, and visual field.

Our results confirm that the oral administration of a calcium channel blocker (nitrendipina) in subjects with moderate essential hypertension and without ocular hypertonia causes systemic effects with a moderate decrease of ocular pressure, while the ocular instillation of the same drug causes a remarkable general hypotensive effect. The scotoma in glaucomatous subjects with normal pressure gets better after the administration of local calcium channel blockers, showing that the peripheral vascular reaction enhances the optical nerve blood flow. The oral administration of β-blockers is also correlated with a reduction of the intraocular pressure, especially if the β-blocker also reduces the systemic blood pressure.

Nadolol, a long half-life, nonselective β-blocker, in a single oral dose of 20 or 40 mg, may result in a remarkable decrease of the intraocular pressure during the whole day. It has been demonstrated that the systemic administration of ACE inhibitors is also effective in reducing intraocular pressure by some mechanisms which, although not known yet, seem to act on the posterior ciliary arteries, shunting the blood to the ciliary body. Finally, acetazolamide, a diuretic usually used to reduce systemic blood pressure, is also able to reduce intraocular pressure. On the other hand, if perfusion pressure is reduced as a consequence of antihypertensive treatment, damage to the visual field could be accelerated.

Keywords Low-tension glaucoma, open-angle glaucoma, antihypertension drug, calcium channel blockers, β-blockers, ACE inhibitors, diuretics.

Tielsh and coworkers1 demonstrated that IOP is more related to low blood pressure than to hypertension. This finding was later confirmed by other studies.12-15 Moreover, it seems that the relation involves DBP; and the strongest relation between systemic blood pressure and chronic simple glaucoma (POAG) is found when DBP is lower than 50 mmHg. A further decrease in the perfusion pressure causes a further increase in the prevalence of POAG. Blood pressure is not the only risk factor for glaucoma, since only 28 percent of glaucoma patients have DBP lower than 50 mmHg.

We can therefore say that data on the correlation between IOP and blood pressure are not conclusive. Some authors found this correlation only in normal pressure glaucoma.4,16,17

Normal pressure glaucoma is characterized by a progressive ipoplasia and atrophy of the optical nerve’s head with progressive visual field loss, similar to POAG but without ocular hypertonia.4,7

In this regard, a recent hypothesis is that normal pressure glaucoma depends on a reduced perfusion of the optical nerve’s head because of vascular diseases or other factors that can influence blood viscosity.18 Epidemiological studies on elderly patients with normal pressure glaucoma evidenced a higher incidence of cerebral ischemia and cardiovascular diseases; these data could explain the ischemic degeneration of the optical nerve.19 Further studies have confirmed the ischemic theory of normal pressure glaucoma, and have taken into account age, presence of diabetes, myocardial infarction, and hypertensive crisis.18,20,21,22 The difference between systemic pressure and intraocular pressure (perfusion pressure) seems much more important than blood pressure per se. Phelps and Corbett22 hypothesized a relation between hemicrania and normal pressure glaucoma, since hemicrania affects 86 percent of the elderly with normal pressure glaucoma, compared to 64 percent of elderly controls, and 95 percent of patients with ocular hypertonia. To some authors hemicrania and glaucoma could share the same pathogenesis, hemicrania being an ischemic disorder. In patients with normal pressure glaucoma, the reduction of diastolic values estimated through ophthalmodynamometry, with or without a decrease in the systolic pressure, suggests a role for perfusion pressure reduction of the optical nerve’s head in glaucomatous damage.23 Antihypertensive treatment could accelerate the loss of the visual field.24,25

In spite of all these researches, little attempt has been made to compare the different therapies through very frequent medical examinations. For these reasons we have performed the present experiments.

Material and Methods

Six hundred patients were enrolled in this experiment. The Ethical Committee of our hospital gave their approval and the patients gave their written informed consent. All experiments were performed according to the guidelines of the Declaration