Ocular vascular occlusive disorders: Natural history of visual outcome

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Abstract

Ocular vascular occlusive disorders collectively constitute the most common cause of visual disability. Before a disease can be managed, it is essential to understand its natural history, so as to be able to assess the likely effectiveness of any intervention. I investigated natural history of visual outcome in prospective studies of 386 eyes with non-arteritic anterior ischemic optic neuropathy (NA-AION), 16 eyes with non-arteritic posterior ischemic optic neuropathy, 697 eyes with central retinal vein occlusion (CRVO), 67 eyes with hemi-CRVO (HCRVO), 216 eyes with branch retinal vein occlusion (BRVO), 260 eyes with central retinal artery occlusion (CRAO), 151 eyes with branch retinal artery occlusion (BRAO) and 61 eyes with cilioretinal artery occlusion (CLRAO). My studies have shown that every one of these disorders consists of multiple distinct clinical sub-categories with different visual findings. When an ocular vascular occlusive disorder is caused by giant cell arteritis, which is an ophthalmic emergency, it would be unethical to do a natural history study of visual outcome in them, because in this case early diagnosis and immediate, intensive high-dose steroid therapy is essential to prevent any further visual loss, not only in the involved eye but also in the fellow, normal eye.

In NA-AION in eyes seen ≤2 weeks after the onset, visual acuity (VA) improved in 41% of those with VA 20/70 or worse, and visual field (VF) improved in 26% of those with moderate to severe VF defect. In non-ischemic CRVO eyes with VA 20/70 or worse, VA improved in 47% and in ischemic CRVO in 23%; moderate to severe VF defect improved in 79% in non-ischemic CRVO and in 27% in ischemic CRVO. In HCRVO, overall findings demonstrated that initial VA and VF defect and the final visual outcome were different in non-ischemic from ischemic HCRVO – much better in the former than the latter. In major BRVO, in eyes with initial VA of 20/70 or worse, VA improved in 69%, and moderate to severe VF defect improved in 52%. In macular BRVO with 20/70 or worse initial VA, it improved in 53%, and initial minimal-mild VF defect was stable or improved in 85%. In various types of CRAO there are significant differences in both initial and final VA and VF defects. In CRAO eyes seen within 7 days of onset and initial VA of counting fingers or worse, VA improved in 82% with transient non-arteritic CRAO, 67% with non-arteritic CRAO with cilioretinal artery sparing, 22% with non-arteritic CRAO. Central VF improved in 39% of transient non-arteritic CRAO, 25% of non-arteritic CRAO with cilioretinal artery sparing and 21% of non-arteritic CRAO. Peripheral VF improved in non-arteritic CRAO in 39% and in transient non-arteritic CRAO in 39%. In transient CRAO, finally peripheral VFs were normal in 93%. In non-arteritic CRAO eyes initially 22% had normal peripheral VF and in the rest it improved in 39%. Final VA of 20/40 or better was seen in 89% of permanent BRAO, and in 100% of transient BRAO and non-arteritic CLRAO. In permanent BRAO eyes, among those seen within 7 days of onset, central VF defect improved in 47% and peripheral VF in 52%, and in transient BRAO central and peripheral VFs were normal at follow-up.

My studies showed that AION, CRVO, BRVO, CRAO and BRAO, each consist of multiple distinct clinical sub-categories with different visual outcome. Contrary to the prevalent impression, these studies on the natural history of visual outcome have shown that there is a statistically significant spontaneous visual improvement in each category. The factors which influence the visual outcome in various ocular vascular occlusive disorders are discussed.

Introduction

Ocular vascular occlusive disorders collectively constitute the most common cause of visual disability in the middle-aged and elderly population, although no age is immune. For their management, the most important piece of information required, from the points of view of both patient and ophthalmologist, is the natural history of visual outcome. This is because information on the natural history of a disease is vital to determine if any treatment modality advocated for these diseases is really beneficial or not. The gold standard is to compare the outcome of treatment with the natural history of the disease. The importance of information about natural history of visual outcome is very well illustrated by the following example. A study of optic nerve sheath decompression for treatment of non-arteritic anterior ischemic optic neuropathy claimed to improve visual loss in this disease – “a disorder without any previously effective therapy” (Sergott et al., 1989). It was considered so important that it was published on an expedited basis by the Archives of Ophthalmology and the procedure became widely popular, till a multicenter clinical trial (Ischemic Optic Neuropathy Decompression Trial, 1995.) showed that it was actually harmful; eyes that had the procedure suffered significantly greater (24%) loss of vision than those left alone (12%). This clinical trial also showed that 32.6% of those who had optic nerve sheath decompression had visual improvement compared with 42.7% of the untreated group. This study concluded that this procedure is “not an appropriate treatment for non-arteritic anterior ischemic optic neuropathy”.

As regards ocular vascular occlusive disorders, in spite of a huge volume of literature that has accumulated on their various aspects over almost 150 years, information on the natural history of their visual outcome is scanty, and when available, it is based on retrospective evaluation, usually of a small number of eyes and often from mixed groups of these disorders (see below). Moreover, the information about visual improvement or deterioration in these studies is not only mostly based on visual acuity (VA) alone but also contradictory and confusing.

I investigated the natural history of visual outcome (of both VA and visual fields) in all these disorders, by prospective studies of large cohorts of patients (Table 1), seen in my Ocular Vascular Clinic at the University of Iowa Hospitals and Clinics in Iowa City since 1973.

Section snippets

Classification of ocular vascular occlusive disorders

To understand visual outcome in ocular vascular occlusive disorders, it is essential to classify these disorders into appropriate categories to get reliable information. My studies have shown that these disorders need to be classified into the following groups and subgroups, as will become evident from the following discussion.

Visual evaluation in my studies

In all my prospective studies dealing with the natural history of visual outcome in various ocular vascular occlusive disorders, visual evaluation involved recording best corrected VA, using the Snellen VA chart, and visual fields with a Goldmann perimeter (using I-2e, I-4e and V-4e targets) in all patients. Amsler grid chart was also used for evaluating central visual field defects; it provides useful information in the evaluation of visual function when the macula is involved. For example,

Natural history of visual outcome in non-arteritic anterior ischemic optic neuropathy

Non-arteritic anterior ischemic optic neuropathy (NA-AION) is one of the most widespread visually disabling diseases in the middle-aged and elderly population, (although no age is immune) (Hayreh et al., 1994a). Information on the natural history of visual outcome is scanty, and when available, it is mostly based on retrospective evaluation. Repka et al. (1983) in 92 eyes with N-AION, after a mean follow-up period of five years, found no improvement or deterioration in VA or visual fields.

Visual outcome in arteritic AION

Arteritic AION is due to giant cell arteritis. Giant cell arteritis is an ophthalmic emergency. It would be unethical to do a natural history study of visual outcome of such a disease, because in this case early diagnosis and immediate, intensive high-dose steroid therapy is essential to prevent any further visual loss, not only in the involved eye but also in the fellow, normal eye. Our studies have shown that in eyes with arteritic AION, when treated with high-dose steroid therapy, only 4% of

Natural history of visual outcome in non-arteritic posterior ischemic optic neuropathy

Compared to non-arteritic anterior ischemic optic neuropathy, this is an uncommon type of ischemic optic neuropathy. The only study dealing with natural history of visual outcome is the one reported by me in 16 eyes (Hayreh, 2004).

Natural history of visual outcome in central retinal vein occlusion

The clinical entity of central retinal vein occlusion (CRVO) has been known since 1878 (Michel, 1878) and it is a common, visually disabling disorder; however, there is little definite information in the literature on the natural history of its visual outcome. It is well-established now that CRVO is of two types: non-ischemic and ischemic CRVO (Hayreh, 1965, Hayreh, 1971, Hayreh, 1976, Hayreh, 1983, Hayreh et al., 1978, Hayreh et al., 1983, Hayreh et al., 1990), with very different visual

Natural history of visual outcome in hemi-central retinal vein occlusion

In 1980, I first described the clinical entity “hemi-central retinal vein occlusion” (HCRVO) (Hayreh and Hayreh, 1980). During embryonic life, there are two trunks of the central retinal vein lying on either side of the central retinal artery (Mann, 1969) (Fig. 5, Fig. 6); one of the two usually disappears before birth, leaving the central retinal vein as a single trunk. However, both trunks persist during postnatal life as a congenital abnormality in 20% of eyes (Chopdar, 1982, Chopdar, 1984,

Natural history of visual outcome in branch retinal vein occlusion

Branch retinal vein occlusion (BRVO) has been known since 1896 (Oeller, 1896); however, there has been conflicting information on its visual outcome. In the available data on the natural history of visual outcome in BRVO, the criterion of VA improvement and study designs vary widely among different studies, so that it is impossible to compare their findings. Rogers et al. (2010) reviewed the natural history of visual outcome in BRVO in articles published in the English language up to 2010, and

Natural history of visual outcome in central retinal artery occlusion

Central retinal artery occlusion (CRAO) has been a well-known clinical entity for almost 150 years (Von Graefe, 1859). A voluminous literature has accumulated on it. Its clinical findings are classical and its diagnosis is easy. A whole host of treatment modalities have been advocated and tried for recovery of visual function, and enthusiastic success has been claimed for treatment after treatment, but none has stood the test of the time. Therefore, the first essential to evaluate beneficial

Natural history of visual outcome in branch retinal artery occlusion

Branch retinal artery occlusion (BRAO) is a common ocular vascular occlusive disorder. It is due to occlusion of a branch of the central retinal artery. In BRAO, as in other ocular vascular occlusive disorders (and indeed, in any disease) it is necessary to know the natural history in order to assess the effectiveness of any therapy. On this topic, I found only three studies with large enough cohorts of patients, published in peer review journals. They were those of Hayreh and Podhajsky (1982)

Classification of cilioretinal artery occlusion (CLRAO)

Cilioretinal artery is a branch of the posterior ciliary artery, arising either directly from the posterior ciliary artery or from the choroid (Hayreh, 1963). Cilioretinal retinal artery occlusion (CLRAO) etiologically is of three distinct types: (i) non-arteritic CLRAO alone (Fig. 23), (ii) arteritic CLRAO associated with giant cell arteritis (Fig. 24) (Hayreh, 1974a, Hayreh, 1990, Hayreh et al., 1998, Hayreh and Zimmerman, 2003b), and (iii) CLRAO associated with central retinal vein occlusion

Choroidal ischemia

This is seen extremely rarely. My experimental studies in rhesus monkeys showed it is due to occlusion of the posterior ciliary artery (Hayreh and Baines, 1972a, Hayreh and Baines, 1972b, Hayreh and Chopdar, 1982). Since posterior ciliary artery also supplies the optic nerve head, it is almost always associated with anterior ischemic optic neuropathy. Thus, in choroidal ischemia the visual loss is primarily due to anterior ischemic optic neuropathy.

Amaurosis fugax in ocular vascular occlusive disorders

Before the onset of visual loss in many of the ocular vascular occlusive disorders, episodes of transient visual blurring may occur. There is little information in the literature about the prevalence of amaurosis fugax in various ocular vascular occlusive disorders, other than in giant cell arteritis with visual loss and ocular ischemic syndrome.

I systematically investigated prevalence of amaurosis fugax separately in each of these disorders in my Ocular Vascular Clinic at the University of

Conclusions and future directions

Ocular vascular occlusive disorders collectively constitute the most common cause of visual disability. Knowledge of the natural history of visual outcome is the primary essential, because information on the natural history of a disease is vital to determine if any treatment modality advocated for these diseases is really beneficial or not. The gold standard is to compare the outcome of treatment with the natural history of the disease.

In the literature, information on the natural history of

Conflict of interest

The author has no conflict of interest.

Acknowledgments

I am grateful to many persons who have contributed in one way or another to the various studies on ocular vascular occlusive disorders over the years. The extraordinary biostatistical expertise of Professor Bridget Zimmerman has been crucial in statistical data analysis. Mrs. Patricia Podhajsky's help with data management for all the clinical studies has been critical. I am grateful to Mrs. Patricia Duffel and Ms. Georgiane Perret for their invaluable help with bibliography, and to my wife

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    Supported by grants EY-1151 and 1576 from the National Institutes of Health, and in part by unrestricted grant from Research to Prevent Blindness, Inc., New York.

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