Ординатура / Офтальмология / Учебные материалы / Retinal Vascular Disease Joussen Springer

Hb Hb type, n number of eyes, More eyes de novo PSR, More sea fans more sea fans per eye, Ai. autoinfarction of sea fans, Vit. hem. vitreous hemorrhage, 7> 11 i.e., 4 more vitreous hemorrhages, Ret. det. retinal detachment in fellow eyes, Av. FU average follow-up in months

Table 27.2.5. Natural course of proliferative sickle retinopathy (PSR)

hemorrhage were the HbSC genotype, the initial presence of vitreous blood, and more than 60 degrees of perfused sea fans [13]. Clarkson [12] followed 11 HbSS (17 eyes) and 11 HbSC patients (19 eyes) with PSR over an average period of 7 years. Progression, either the increase in number or extent of sea fans or progression to vitreous hemorrhage, was more common in HbSC patients.

Downes [30] reported the 20-year longitudinal observation data of the Jamaican cohort of 307 HbSS

and 166 HbSC patients. Patients with unilateral PSR had a 16 % (11 % in SS, 17 % in SC) probability of regressing to no PSR and a 14 % probability (16 % in SS, 13 % in SC) of progressing to bilateral PSR. Those with bilateral PSR had a 8 % (for SS and SC) probability of regressing to unilateral PSR and a 1 % (0 % in SS, 2 % in SC) probability of regressing to a PSR-free state.

27.2.8.5 Clinical Correlations

Research that attempted to determine factors correlating with the clinical course was performed primarily in Jamaica by Serjeant and his coworkers. Investigating hematologic indices in a group of 261 HbSS patients, of whom 29 had developed PSR, Hayes et al. [51, 52] found a high Hb level (> 9 g/dl) and a low HbF level (< 5 %) constituted a risk factor for PSR in males only. Among 243 HbSC patients of whom 90 had developed PSR, Hayes [51, 52] found a high mean cell hemoglobin concentration in males and a low fetal hemoglobin concentration in both sexes to be significantly more common in PSR.

PSR was more frequently (14 %) found in HbSS patients 40 years of age and older. PSR was observed to develop most often between the ages of 20 and 30 years; 68 % of HbSC patients aged 45 years or over were affected.

Talbot et al. [105] reporting on the 59 HbSS and 37 HbSC children ranging from 5 to 7 years old (cohort) found retinal closure to be consistently more common in HbSS children; however, this difference did not reach statistical significance. In the same cohort, Talbot et al. [103, 104] found that retinal closure was closely correlated with low total hemoglobin concentration and fetal hemoglobin concentration, high reticulocyte and irreversibly sickled cell (ISC) counts in HbSS disease and with high reticulocyte counts in HbSC disease. There was no apparent relationship between vessel closure and clinical events including dactylitis, pneumonia, sickle crisis and infarction, gastroenteritis, weight loss and fever in either genotype. In a follow-up report on the same cohort 6 years later, these observations held true [102].

In both SS and SC patients, BE Serjeant et al. [95, 96, 98] compared plasma and serum viscosity, whole blood viscosity and erythrocyte filterability in ageand sex-matched pairs with or without PSR (27 HbSS pairs, 31 HbSC pairs). HbSC patients with PSR showed significantly higher mean cell hemoglobin and lower HbF levels; however, the viscosity and erythrocyte filtration indices did not differ between the two groups. HbSS patients with PSR showed a higher Hb and lower HbF in males and a higher mean cell hemoglobin concentration in females. In males with PSR, significantly higher whole blood viscosity was measured at high shear and at the patient’s own hematocrit.

Electroretinograms from patients with PSR showed reduced a-wave, b-wave and oscillatory potential amplitudes, possibly due to photoreceptor dysfunction secondary to choroidal ischemia or increased oxygen demands by the inner retina [81, 82]. Ischemia of the inner retina may also have contributed to the altered b-wave and oscillatory poten-

tials. The same group [38] found a negative correlation between the ERG amplitude measurements and capillary non-perfusion.

In summary, although the most active phase of PSR was between 20 and 30 years of age, there appears to be a cumulative effect with age. Factors that increase sickling per cell (such as a high mean

cell hemoglobin concentration and low HbF) and red III 27 cell numbers (such as HbSC) lead more frequently to

PSR. The most prominent correlation is that between PSR and HbSC.

No reports have indicated that peripheral closure is clearly more extensive in HbSC than HbSS patients. Indeed, in the children’s cohort the reverse was shown. To try and explain the different incidence of PSR in HbSS and HbSC patients, BE Serjeant et al. [95, 96, 98] and GR Serjeant [26] hypothesized that, due to the high obstructive tendency in HbSS, there would be a high prevalence of retinal infarction, in addition to early autoinfarction of developing neovascular tissue. In HbSC retinal infarction would develop; however, due to the moderate vaso-occlu- sive tendency in HbSC autoinfarction of neovascularizations would be rare. An alternative hypothesis by Serjeant [26] postulates that the greater vaso-occlu- sion in HbSS disease results in infarcted retina, which fails to release a vaso-proliferative substance, whereas the lower vaso-occlusion in HbSC disease might allow for the persistence of ischemic retina.

Van Meurs [109] showed in adult patients that the border between perfused and non-perfused retina was more peripheral in HbSS patients than in HbSC patients and suggested therefore that the greater area of non-perfused ischemic retina in HbSC patients explained the greater prevalence of PSR.

Penman [83] found that the development of PSR was dependent on the type of peripheral vascular border, i.e., patients without continuous arteriovenous loops and with capillary buds or stumps extending into non-perfused retina (type IIb, more prevalent in HbSC patients) were at greater risk for PSR. In a study in Saudi Arabia, Al-Hazza found that patients with the Benin haplotype of HbS (as in Jamaica) had such a type IIb border more frequently than patients with the Asiac haplotype [4].

27.2.8.6Differential Diagnosis of Proliferative Sickle Retinopathy

The typical aspect of retinal neovascularizations in sickle cell patients renders the differential diagnosis list restricted. By “typical” we mean: an area of peripheral non-perfusion with neovascular formations bordering its posterior boundary, often already sea fan-like, either isolated or connected in ridges, some parts already partly fibrosed. Apart from

27 III

Fig. 27.2.10. Equatorial area in a 20-year-old Caucasian male with FEVR. Note the notch of extra non-perfusion between superior and inferior temporal vasculature and the abnormal parallel orientation of vessels due to the abnormal development of the retinal vascular network. (Courtesy of Eric van Nouhuys, MD)

branch vein occlusion, Eales’ disease, retinopathy of prematurity and familial exudative vitreoretinopathy may be considered.

In regressed retinopathy of prematurity (ROP) [34a] and dominant exudative vitreoretinopathy (DEVR or FEVR) [111], the areas of non-perfusion are more anterior than in PSR. In PSR the perfusednonperfused retina border is highly irregular, reflecting the ongoing centripetal process of vasoocclusion; consequently, sea fans are generally not equidistant to the disk, as is usually the case in ROP and DEVR, where vascular development was impaired at one point in time. Similarly, there is no V-shaped border of perfused retina formed by the arrested growth of superior and inferior temporal arcades as in DEVR (Fig. 27.2.10). The features associated with retinopathy in incontinentia pigmenti are female sex, cutaneous manifestations, dental abnormalities and presentation at a generally younger age than PSR.

The most common diagnosis of exclusion is Eales’ disease (Fig. 27.2.11). The clinical definition of Eales’ disease is not yet well delineated. Elliot [32] and Renie et al. [88], in series of 30 cases each, include vasculitis or periphlebitis, together with peripheral occlusive vascular disease, within its definition. In these authors’ view, vasculitis would be an early event in the course of Eales’ disease, explaining the lack of inflammatory signs in many patients. Spitz-

Fig. 27.2.11. Peripheral capillary non-perfusion and retinal neovascularization with fibrotic parts in a 50-year-old Caucasian patient diagnosed with Eales’ disease

nas [100], however, studying over 300 patients in Essen, considered periphlebitis and papillitis to be part of a separate entity: idiopathic periphlebitis, and reserved the term Eales’ disease for the noninflammatory peripheral obstructive vasculopathy, which resembles PSR in many ways. An important consideration was not to confuse the vascular sheathing (opacification of the vessel wall, hyaline degeneration [75]), as seen in Eales’ disease and sickle cell disease, with the more irregular and wider inflammatory sheathing known to occur in vasculitis.

Obviously, in the diagnostic workup of each person of predominantly African (or Mediterranean or Middle Eastern) extraction with peripheral retinal vascular obstructions or neovascularization, a sickle cell test and hemoglobin electrophoresis are mandatory and conclusive. Any other positive finding revealed from the work-up might only suggest a joint pathological effect, which may be difficult to assess in terms of its relative impact. Interestingly, this issue has not been addressed in connection with HbSS, HbS--thal or HbSC disease. However, the combination of HbAS and diabetes [61, 78], active luetic disease, lupus erythematodes, or tuberculosis [78] has been reported in seven patients; the relative contribution of each disease to retinal neovascularization remains speculative. In the other reports on PSR and sickle cell trait patients (Rubinstein, 1967, two cases [91]; Welch et al. [114] and Treister et al. [106], one case each), no effort was made to exclude Hb S-- thal-plus or other causes. In patients with HbAC

(whose erythrocytes do not sickle, but have a higher MCHC) and diabetes, four patients with PSR-like fundus findings have been reported [59, 61].

27.2.9 Prophylactic Treatment of PSR

Hannon [49] successfully closed retinal neovascularizations with diathermy in two sickle cell patients. Condon et al. [21] used the xenon arc for this purpose, treating both the feeder vessels and the sea fan itself. Laser photocoagulation was initially used to treat the feeder vessels [13, 47, 48, 60], and later used in a scatter fashion around and peripheral to the neovascularizations [27, 34, 35, 87]. Cryocoagulation has rarely been administered [69]. Seibert mentioned the possibility of using transscleral diode laser treatment [94].

27.2.9.1 Reports

The feeder vessel technique has proven very successful in stopping perfusion of neovascularizations, as shown on fluorescein angiography [21, 47, 62] (Fig. 27.2.12a, b).

Apart from the retinal breaks [24, 43], a surpris-

ingly high incidence of choroidal neovascularization III 27 has been reported after treatment of feeder vessels,

for which high energy levels must be used to close the feeding artery. Choriovitreal neovascularizations often bled and proved very difficult to close with photocoagulation [16, 17, 29] (Fig. 27.2.13).

Due to the high energy settings used in the feeder vessel technique, choroidal arteries can become occluded, which results in choroidal ischemia. This shows initially as triangular grayish-white patches anterior to the treatment site, later fading into a similarly shaped region of granular hyperpigmentation

27 III

Fig. 27.2.14. Despite a fair amount of scatter laser coagulation, this sea fan remained perfused in a 41-year-old HbSC patient

[43]. Functionally, this resulted in subtle changes of the peripheral visual fields only.

Even with use of the highly effective feeder vessel technique, it was difficult to show a clinically significant effect in a prospective, randomized trial [14, 62]. This is caused partly by the introduction of a potentially sight-threatening complication, such as retinal breaks or choriovitreal neovascularization, and partly by the (relative to the period of observation) slowly progressive nature of sickle cell retinopathy.

The scatter technique caused few complications, but proved much less effective in the closure of sea fans, particularly elevated ones with fibrous tissue [87] (Fig. 27.2.14).

In a prospective randomized controlled study of scatter treatment of patients on Jamaica, Farber et al. [34] reported a statistically significant reduction in visual loss of more than 3 months duration as well as in the number of vitreous hemorrhages. Clarkson [12], however, points out that there is no difference in the occurrence of permanent reduction in vision between the treated group and controls. Therefore, because of the marginal benefit on visual function and the tendency of sea fans to autoinfarct, prophylactic laser is not advised by some experts [12, 30].

27.2.10 Epiretinal Membranes

Moriarty et al. [77] found epiretinal membranes (ERMs) in 25 eyes (22 HbSC, 3 HbSS patients) of the 699 examined eyes (3.6 %). All eyes with ERMs had PSR.

Carney et al. [11] detected epiretinal membranes in 55 of the 1,486 eyes for which fundus photographs were available (40 HbSC, 13 HbSS, 2 HbSthal) (3.7 %). The macula was involved in all but four eyes. In only six (HbSS) eyes there was no coexistent PSR. In one eye the pucker spontaneously peeled.

Hrisomalos et al. [60] reported on six eyes, in which vitreous bands exerted traction on the retina.

27.2.10.1 Etiology

Previous vitrectomy or detachment surgery had been performed in three of 55 eyes with ERMs [11]. In Carney’s series there was an equal number of photocoagulated and untreated cases and in Hrisomanos’ cases only one eye had been treated; the other five were control cases in treatment trials. In Moriarty’s series epiretinal membranes were significantly less common in treated PSR eyes.

Thus, surgery and photocoagulation cannot be implicated in the genesis of these membranes, but rather the presence of neovascularization with its coexistent vitreoretinal changes. Transudation of plasma from PSR lesions may disorganize the cortical vitreous; the resulting posterior detachment may disrupt the internal limiting membrane, thus providing access for glial cell ingrowth [62] either along the retinal surface or onto the retracting, collapsing vitreous face, with secondary contraction of transformed retinal epithelial cells [68].

27.2.10.2 Relevance to Function

In 40 % of Moriarty’s cases, visual acuity of less than 6/18 was due to epiretinal membranes; in two cases poor acuity was due to tractional retinal detachment. In nine of Carney’s cases, moderat visual loss was caused specifically by the membranes; however, this was not the case in six patients demonstrating severe visual loss.

Carney et al. [11] reported visual improvement in one case following vitrectomy and membrane dissection. Hrisomalos et al. [60] reported usage of the neodymium-YAG laser in cutting vitreous bands. In three eyes, retinal traction appeared to be stabilized after treatment; in two of these, additional vitrectomy and membrane peeling were required.

Epiretinal membranes appear to be a common cause for a modest decrease of vision in patients with PSR. Given the uncertainty of visual improvement and the perioperative risk, an indication for vitrectomy has to be weighed against the possible benefits of epiretinal membrane removal, i.e., the restoration of binocular function.

27.2.11 Macular Holes

Few patients with macular holes in association with sickle cell disease have been reported [74, 85]. In these patients, macular holes were all associated with proliferative sickle retinopathy; the macular holes had a more distorted shape, more epiretinal tissue surrounding the macular hole and occurred at a much younger age than in patients with idiopathic macular holes. These macular holes are likely to be

the result of more extended tangential traction as part of proliferative sickle retinopathy, very much like epiretinal membranes in these patients (Fig. 27.2.14).

Mason [74] described the successful closure of such a macular hole with an improvement in vision from 20/400 to 20/40.

27.2.12Treatment of Vitreous Hemorrhages and Retinal Detachments

Non-resorbing dense vitreous hemorrhages and retinal detachments (tractional or rhegmatogenous, or both), sometimes associated with vitreous hemorrhage, have been treated either with ab externo detachment surgery (exoplants, encircling bands, cryocoagulation, external drainage), with intraocular surgery (vitrectomy, membranectomy, internal drainage), or by a combination of these. In patients with sickling disorders, these operations have proven to have a high percentage of intraand postoperative complications.

27.2.12.1 Anterior Segment Ischemia

The anterior segment ischemia syndrome (ASI) can comprise keratopathy, intraocular inflammation with severe pain, cataract formation and hypotony. The syndrome in its most severe form can lead to

phthisis bulbi and enucleation. Originally it was associated with detachment surgery involving diathermy, detachment of rectus muscles and tight encircling elements [8, 115] or with strabismus surgery on three or more muscles per eye [41]. Histological studies have revealed necrosis of parts of the iris and ciliary body [8, 115] resulting from interruption

of either the long posterior ciliary arteries or the III 27 anterior ciliary arteries.

Ryan et al. [92] described the syndrome in six out of nine HbSC patients who underwent detachment surgery. Since he was unable to correlate this high incidence of ASI consistently with the previously cited risk factors, Ryan identified the hemoglobinopathy itself as one such factor. Obviously, any interference with blood flow and supply to the anterior segment can induce sickling and increase the risk of anterior segment ischemia. Leen [70] reported peroperative hypotension during general anesthesia as a possible cause, as well as laser coagulation over the long posterior ciliary arteries.

27.2.12.2 Surgical Reports

Surgical procedures, outcome and complications in surgical treatment reports are presented in Table 27.2.6. In 14 cases, eyes lost their function [light perception (LP) positive or negative, hand movements only (HM)]. In six of the 11 reported

Table 27.2.6. Results and complications of external retinal detachment surgery and vitrectomy in PSR

Ext. external approach, Mu. rectus muscle disinsertion, En. encircling band, Vit. vitrectomy, An./fu. success anatomic or functional success, TRD traction retinal detachment, RD retinal detachment, Tear retinal tear, ASI anterior segment ischemia, LP light perception, HM hand movement, SG secondary glaucoma, Tran. exchange blood transfusion, Combined both external approach and vitrectomy

27.2.12.4Measures to Consider in Vitreoretinal Surgery

As there is no evidence-based information available, the following perioperative measures appear rational to us.

Local anesthesia with additional oxygen is preferable over general anesthesia, to decrease the chance of peroperative hypotension and postoperative sickle cell crises.

Try to interfere as little as possible with the recti muscle and do not apply an encircling band, to decrease the risk of anterior segment ischemia. Try to avoid applying heavy laser coagulation over the long posterior ciliary arteries.

27.2.13.1 Reports

We have included optic atrophy due to local vascular compromise as due to sickle cell disease, which may be controversial. In one of Asdourian et al.’s [6] patients, luetic serology was positive. One 27-year- old HbSS patient had no light perception in either eye, due to cortical blindness following severe circulatory shock and respiratory arrest after intraabdominal blood loss following a cholecystectomy.

The complications of proliferative retinopathy, i.e., vitreous hemorrhage, retinal detachment, epiretinal membranes and anterior segment ischemia prove to be the major cause of visual loss: 82 % (Tables 27.2.7, 27.2.8).

n number of patients reported, Hb hemoglobin type, CAO central retinal artery occlusion, Opt. a. optic atrophy, Mac. a. macular arteriole, Vitr. hem. vitreous hemorrhage, Cil. a. ciliary artery occlusion, CVO central vein occlusion, SG secondary glaucoma, VH vitreous hemorrhage, RD retinal detachment, Epi. epiretinal macular pucker, ASI anterior segment ischemia, 0.1 visual acuity of 6/ 60 or 20/200, CF counting fingers, HM hand movements, LP light perception, x “loss of vision” or “reduced visual acuity” not specified, but in association with retinal detachment

a Surgery series, b Prophylactic treatment series, c Patients referred to in other reports as well

729

III 27

730

27 III

III Pathology, Clinical Course and Treatment of Retinal Vascular Diseases

Table 27.2.7. (Cont.)

n number of patients reported, Hb hemoglobin type, CAO central retinal artery occlusion, Opt. a. optic atrophy, Mac. a. macular arteriole, Vitr. hem. vitreous hemorrhage, Cil. a. ciliary artery occlusion, CVO central vein occlusion, SG secondary glaucoma, VH vitreous hemorrhage, RD retinal detachment, Epi. epiretinal macular pucker, ASI anterior segment ischemia, 0.1 visual acuity of 6/ 60 or 20/200, CF counting fingers, HM hand movements, LP light perception, x “loss of vision” or “reduced visual acuity” not specified, but in association with retinal detachment

a Surgery series, b Prophylactic treatment series, c Patients referred to in other reports as well

731

III 27