Nanophthalmos A New Clinical

With Uveal Effusion

Entity

Robert J. Brockhurst, MD

\s=b\ Five patients exhibited the association of nanophthalmos and uveal effusion, apparently on a familial basis. Glaucoma, occurring in the fourth to sixth decades of life, required surgical intervention that was followed by the development of secondary retinal and choroidal detachment. Recognition of this syndrome is important because: (1) surgical procedures for glaucoma should be avoided, if possible, in order to prevent the development of uveal effusion; (2) retinal detachment surgical procedures are ineffective in uveal effusion and should be avoided, and (3) choroidal elevation occurring in the uveal effusion phase may be erroneously diagnosed as an intraocular tumor and unnecessary enucleation may follow.

(Aren Ophthalmol 93:1289-1299, 1975)

Submitted for publication June 27, 1974. From the Department of Retina Research, Retina Foundation and the Retina Associates, Boston. This paper was accepted as a thesis in partial fulfillment of the requirements for membership in the American Ophthalmological Society. Reprint requests to Department of Retina Research, Retina Foundation and the Retina Associates, 100 Charles River Plaza, Boston, MA 02114 (Dr Brockhurst).

In degrees

contrast to

high myopia, high

of hyperopia have re¬ ceived little attention in the ophthal¬ mic literature. In 1924, Black1 de¬ scribed twin sisters, aged 28 years, who showed hyperopia of approxi¬ mately 7 diopters in both eyes. In 1950, Southgate- described two chil¬ dren, aged 6 and 12 years, whose hyperopic errors were 15 D and 17 D, respectively. Neither Black nor Southgate noted any other abnormalities or ocular disorders such as microphthalmia, glaucoma, or retinal de¬ tachment. In 1951, Witmer3 first re¬ ported the association of retinal detachment with high degrees of hy¬ peropia. In two patients, he observed hyperopic errors of 12 to 15 D. The retinal detachments were character¬ ized by a yellowish discoloration of the retina, and in neither case was he able to demonstrate a retinal break. Surgery failed to reattach the de¬ tached retinas. In 1952, Hatcher' reported the case of a 9-year-old girl, with a refractive error of +21 D in the right eye and + 20 D in the left. Glaucoma was present in each eye. The corneal diameters were 10 mm, 11.75 mm being considered normal for her age. In 1953, Manning5 reported the asso¬ ciation of high hyperopia with corneal vascularization; he quoted Braley as having observed a case of high hyper¬ opia that later developed a "solid"

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retinal detachment. This suggests that the retinal elevation may have been accompanied by, or due to, choroidal detachment. In 1955, Rathschfiler and Dufour" reported three cases of high hyper¬ opia associated with fundus problems. In one patient, whose refractive error was +14 D in both eyes, there was apparent an idiopathic retinal detach¬ ment in one eye. The other two pa¬ tients, who had histories of pulmo¬ nary disease, showed hyperopia of +8 D and +10 D, as well as evidence of periphlebitis, retinitis proliferans. and vitreous hemorrhage. There is a distinct possibility that these cases may have been examples of Eales dis¬

occurring in hyperopic eyes. In 1959, Vetter7 reported on the as¬ sociation of microphthalmia, glau¬ coma, and retinal detachment. His re¬ port included four patients with chronic glaucoma with retinal detach¬ ment and one patient with microph¬ thalmia with retinal detachment. Ap¬ parently, the retinal detachments were rhegmatogenous in nature, as retinal breaks were found. Unfortu¬ nately, the refractive error of the microphthalmic patient was not re¬ corded. Of the four other patients with glaucoma, two were emmetropie and two were myopic. In 1963, Zuccoli" reported two cases of hyperopia ( + 6 D and +10 D) oc¬ curring in men, and associated with ease

Fig 1.—Right eye of patient 1 showing total secondary retinal detachment with¬ out breaks and peripheral annular choroi¬ dal detachment.

Fig 2.—Right fundus of patient 1 two months after systemic steroid treatment. Note absorbed subretinal fluid, except for that located temporal to the macula. Choroidal detachment persisted.

Fig 3.—Polyethylene 90 tubing, which had been used as an equatorial encircling element in the right eye of case 1. Length of encircling element was 47 mm, indicat¬ ing diameter of globe as approximately 15 mm.

Fig 4.—Fundus of right eye of patient 2 showing an inferior secondary retinal de¬

Fig 5.—Fundus of right eye of patient 3 showing peripheral annular choroidal de¬

Fig 6.—Fundus Secondary retinal

temporal cysts of the retina. How¬ ever, his patients did not show any retinal detachment, or glaucoma, and the fundus picture suggests the possi¬ bility of retinoschisis. Microphthalmia is a general term that includes a wide variety of dis¬ orders sharing one common finding: an eye smaller than normal. Many microphthalmic patients character¬ istically show other developmental anomalies of the eye or body. For ex¬ ample, microphthalmia may be very severe, resulting in such a small, dis¬ organized eye that no ocular structure is visible: anophthalmia. In other

cases,

microphthalmia is frequently complicated by developmental defects of the fetal fissure, and coloboma of the iris, choroid, and retina is present.

gross

tachment with intraretinal exudates. Choroidal detachment was present in up¬ per nasal and upper temporal quadrants.

tachment.

Sometimes it is associated with den¬ tal, skeletal, cardiovascular, and uro¬ genital developmental defects. In contrast to the forms of mi¬ crophthalmia that are associated with other ocular or systemic develop¬ mental abnormalities, there is a pure form of microphthalmia that has been referred to pure

nanophthalmos.0 In microphthalmia, or nanoph¬ as

thalmos, the eye is small in dimen¬ sion, but it is not affected by other

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of left eye of patient 3. detachment and periph¬ eral choroidal detachment are evident.

developmental defects nor is it accompanied by other systemic devel¬ opmental defects. The nanophthalmic eye is typically reduced in volume without other apparent abnormality. The palpebrai fissure is narrow and the eye appears deeply set in it's or¬ bit. Hyperopia of approximately +18 D is common. The eyeball diameter varies from 14 to 17 mm, and fre¬ quently glaucoma is present. The pre¬

disposition

to

glaucoma apparently

results from the presence of a rela¬ tively normal-sized lens that embar¬ rasses the filtration meshwork. Both dominant and recessive forms of he-

Fig 7.—Fundus of left eye of patient 4. A secondary retinal detachment was

total

present and choroidal detachment noted

interiorly under the detached

was

retina.

Fig 8.—Left fundus of patient 4 after drainage of most subretinal fluid. Incar¬ ceration of retina occurred at drainage

site at 4 o'clock. Choroidal elevation was then better visualized and was especially

prominent nasally.

in nanophthalmos have been described. In medicine, the constant associa¬ tion of several apparently unrelated abnormalities suggests a common de¬ nominator, or syndrome. This report describes five patients who show a clinical syndrome characterized by the association of pure microph¬ thalmia, or nanophthalmos and uveal effusion.10 To my knowledge, this has not been reported previously. The features shown include small eyes with thick sclera, high degrees of hy¬ peropia, glaucoma, and choroidal ele¬ vation with retinal detachment of the secondary (nonrhegmatogenous)

redity

type. REPORT OF CASES an only child with +13 hypermetropia, first developed acute angle closure glaucoma in the left eye at age 30 years. Family eye history was not impressive. Following glaucoma surgery, the left eye developed malignant glaucoma

Case 1.—A man,

D

and became blind. At the age of 47, acute angle closure glaucoma occurred in the right eye, the intraocular pressure measur¬ ing 65 mm Hg with a closed filtration

angle.

iridectomy and lens extraction performed. Two days after this pro¬ cedure, an annular, peripheral choroidal detachment and temporal retinal detach¬ ment extending into the macula were ob¬ A sector

were

served. No retinal break could be observed.

diameter is 10

Three months later, the choroidal detach¬ ment was considerably smaller, but the retina remained detached in the temporal

periphery, extending slightly posterior

Fig 9.—Right eye of patient 5. Note ab¬ of inflammatory signs, eye being completely white. Additional surgical colo¬ boma present at 6 o'clock, performed at time of cataract extraction by inferior route. Eye sets deeply in orbit; corneal sence

to

the equator. Two years later, in 1957, cen¬ tral vision failed in the right eye. Results of examination showed cor¬ rected vision limited to hand movements at 0.6 meters (2 ft) in the right eye with cor¬ rection of +21 D sphere (aphakic). In¬ traocular pressure was 20 mm Hg. The cornea measured 10.5 mm in diameter hor¬ izontally. A sector coloboma was observed at 12 o'clock and gonioscopy revealed the angle to be very narrow with many periph¬ eral synechiae. No keratic precipitates, aqueous flare, or cells were seen. The ret¬ ina was totally detached, with the fluid shifting to a dependent position, and show¬ ing smooth high balloons without any evi¬ dence of a retinal break (Fig 1). There was a diffuse annular choroidal detachment in the periphery. Ocular tonography revealed a coefficient of outflow of 0.05 in the right eye.

The left eye was blind, with an ocular tension that measured 70 mm Hg. Corneal edema was present, the anterior chamber appeared flat, and the angle was closed. A moderate flare was present in the aqueous humor and a sector coloboma was present superiorly, with the pillars of the iris ad¬ herent to the posterior surface of the cornea. Corneal vascularization was noted superiorly in the region of the coloboma. A mature cataract precluded examination of the fundus. Results of general physical evaluation were within normal limits, as were the results of laboratory studies for

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mm.

uveitis. Examination of the cerebrospinal fluid (CSF), however, revealed an elevated total protein level of 68 mg/100 ml but no cells were found. The upper limit of a nor¬ mal protein level is 45 mg/100 ml. Subretinal fluid was drained and an en¬ circling polyethylene tube (No. 90) was placed around the right globe to restore in¬ traocular pressure. Following surgery the retina partially reattached, but no retinal breaks could be discovered. During sur¬ gery, the diameter of the globe was found to measure 16 mm and the sclera measured 2.5 mm in thickness at the site of the sclerotomy just posterior to the equator. Analysis of the subretinal fluid, which was drained at operation, revealed the absence of hyaluronic acid. Such a finding indicates that no fluid vitreous is present in the subretinal fluid and is almost certain evi¬ dence that no retinal break exists.1"1-' The clinical diagnosis of secondary reti¬ nal detachment was thus confirmed, and the patient was treated with prednisone. The dosage was 40 mg/day for one month and then was reduced to 30 mg/day. After two months of treatment, the retina be¬ came reattached, except for a residual area temporal to the macula. However, the choroidal detachment persisted (Fig 2). Prednisone dosage was reduced to 20 mg/day; two months later the retinal de¬ tachment lessened, involving only the tem¬ poral periphery. Vision, which had been limited to hand movements at 0.3 meters (1 ft), improved to 20/300. During the next ten years, the temporal detachment occa¬ sionally increased in extent but responded to periodic courses of systemic steroid

treatment. In every way, this retinal de¬ tachment resembled that observed in uveal effusion.1" In 1969, when the patient was 61 years of age, the retinal detachment be¬ came more

and vision

extensive, invaded the macula,

was

reduced to hand movements

again. Since the detachment proved to be refractory to systemic steroids, a sec¬ ond subretinal fluid drainage was per¬ formed. The encircling tube, which had been inserted 14 years before, was re¬ once

moved. Its circumference was 47 mm, indi¬ cating a diameter of the globe of 15 mm (Fig 3). Fluid gradually returned, and an¬ other subretinal fluid drainage was per¬ formed six months later. Since that time, a peripheral secondary retinal detachment has persisted despite systemic steroid therapy. Although the intraocular pressure has been well controlled with acetazolamide and local medication, the visual field has gradually become limited to a small temporal island of vision 10 degrees in diameter. The important features illustrated by this case are high hyperopia, small cornea size, small ocular dimensions with a very thick sclera, glaucoma with narrow fil¬ tration angle, choroidal detachment, and secondary retinal detachment. The CSF showed no lymphocytosis, but the total protein level was elevated. It appears that the choroidal elevation and retinal detach¬ ment represent uveal effusion1" occurring in an extremely small hyperopic eye that has developed glaucoma as its first serious ocular problem. Case 2.—A man, age 51 years, with a high hyperope measuring OD +13.75 S2.00 ex 180° and OS +14.50 S-2.00 ex 180°, suddenly developed acute angle closure glaucoma in his right eye, with the in¬ traocular tension measuring 55 mm Hg. There was no family history of any ge¬ netic, ocular, or systemic disorder at this time. The acute attack of glaucoma in the right eye was treated surgically by a sec¬ tor iridectomy. Because the left eye showed an extremely narrow angle and a slight elevation of intraocular pressure measuring 28 mm Hg, a peripheral iridec¬ tomy was done. Two years later, an infe¬ rior retinal detachment occurred in the left eye, which failed to reattach after retinal surgery. A few months later, a retinal de¬ tachment also occurred in the right eye. On examination in 1960, corrected vision measured 20/200 in the right eye and re¬ vealed bare light perception in the left. The right eye showed a corneal diameter of 10 mm, early band keratopathy, a very shallow anterior chamber angle with many peripheral anterior synechiae, elevated in¬ traocular pressure of 32 mm Hg, a sector coloboma at 12 o'clock, and early periph-

Fig 10.—Right fundus of patient 5 showing marked elevation of choroid posteriorly, pecially nasal to the disc.

es¬

eral cortical lens opacities. The eye ap¬ peared white and was free of signs of in¬ flammation. The vitreous was clear and showed no inflammatory cells. An inferior, secondary retinal detachment with many intraretinal exudates, but with no observ¬ able retinal breaks, was present. Choroidal detachment was also observed in the upper temporal and upper nasal quadrants (Fig

4).

The left eye showed a corneal diameter of 10 mm, intraocular pressure of 6 mm Hg, folds in Descemet membrane, early band keratopathy, a narrow angle that was completely closed, a small peripheral surgical coloboma at 12 o'clock, marked iris atrophy, seclusion of the pupil, and an im¬ mature cataract. A slight flare without cells was present in the aqueous humor. The fundus could not be visualized, even with indirect ophthalmoscopy. The retinal detachment in the right eye was considered not to be rhegmatogenous, and an extensive medical and conventional uveitis work-up was performed. Results of all studies were normal, with the exception of the CSF studies, which showed an ele¬ vated total protein level of 73 mg/100 ml without lymphocytosis. The results of se¬ rum electrophoresis were normal. The pa¬ tient was treated with prednisone given orally, 125 mg/day in a single dose for three days; this was later reduced to 100 mg/day for one week, and then to 100 mg every other day. Two weeks after the onset

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Fig 11 .—Fundus of right eye of patient 5. Note elevated choroidal detachment in the periphery.

Fig 12.—Anterior segment of left eye of patient 5. Eye is white and free of in¬ flammatory signs; corneal diameter is 10 mm.

Fig 13.—Left fundus of patient 5 reveal¬ ing diffuse choroidal detachment mark¬ edly elevated in periphery in all quadrants.

Fig 14.— -scan ultrasonography of eyes of patient 5. (left), anteroposterior axial length is 16.5 mm and 17.0

In right eye (right) and left eye mm, respectively.

Note smooth flat retinal detachment.

of therapy, vision had improved to 20/70 and the retinal detachment had begun to subside. One month later, the retina was almost completely reattached and the prednisone dosage was reduced to 75 mg every other day. Control of intraocular pressure was not satisfactory, in spite of acetazolamide administered orally and the local installation of pilocarpine drops. At this time, the patient returned home (abroad). One month later, he suddenly died; the exact cause of death was not de¬ termined. Unfortunately, postmortem ex¬ amination and histological studies of the

eyes were not performed. This case shows high hyperopia associ¬ ated with angle closure glaucoma, choroi¬ dal detachment, secondary retinal detach¬ ment, and an elevated total protein level in the CSF. As in the first patient, patient 2 demonstrates the association of uveal effu¬ sion with high hyperopia, angle closure glaucoma being the first symptom of this serious ocular disease. Case 3.—In 1965, a woman, aged 43 years, sister of the patient described in case 2, with + 13 D hyperopia, devel¬ oped acute angle closure glaucoma in the left eye, with ocular tension measuring 65 mm Hg. After eight months of miotic ther¬ apy, the tension remained elevated at 30 mm Hg; therefore, trephination was per¬ formed. One week after this procedure the retina detached. A review of the family history showed that only the patient and her brother (case 2) were hyperopic. There was no history of other members of the family suffering any significant ocular dis¬ order. Findings from general medical eval-

Fig 15.—B-scan ultrasonography of left eye of patient 5. Note generalized elevation of choroid throughout fundus, especially near equatorial region and in area of pars plana. uation and uveitis survey were not re¬ markable. Cerebrospinal fluid examination revealed a normal total protein level of 31 mg%/100 ml and the absence of any cells. Ocular examination revealed corrected vision to be 20/30 in the right eye and hand movements at 1.2 meters (4 ft) in the left eye. The right eye showed no signs of in¬ flammation, a clear cornea measuring 10 mm in diameter, a very narrow angle in which the trabeculum could not be ob¬ served, ocular tension of 9 mm Hg, a clear lens, and peripheral choroidal detachment (Fig 5). A visual field examination showed no defect in the right eye (Goldmann IV-2

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test

object).

The left eye showed a small cornea, mea¬ suring 10 mm, a peripheral surgical colo¬ boma at 12 o'clock with a filtering cicatrix, ocular tension of 10 mm Hg, and a very shallow anterior chamber, although the trabecular area could be seen. A slight flare without cells was present in the aqueous humor. Peripheral synechiae were noted near the iridectomy and many poste¬ rior synechiae were present, resulting in a small bound down pupil. The lens was clear, and fundus examination showed a total retinal detachment. Since ophthal¬ moscopy was difficult, due to the miotic pu-

pil,

and since

no

retinal break could be

iridectomy was performed. Following this procedure, the fundus could be better evaluated and a peripheral found,

a

sector

choroidal detachment, as well as a second¬ ary type retinal detachment without breaks, was diagnosed (Fig 6). The patient was treated with prednisone administered orally, 40 mg/day for two months, follow¬ ing which the dose was reduced to 10 mg/day. After four months, the retina be¬ came reattached. Vision improved to 20/400. The peripheral choroidal detach¬ ment persisted in both eyes. Patient 3 demonstrates the association between high hyperopia, angle closure glaucoma, choroidal detachment, and sec¬ ondary retinal detachment, which re¬ sponded to steroid therapy. In addition, a familial predisposition to this unusual problem is evident in patients 2 and 3. Case 4.—A man, +18 D hyperope, devel¬ oped acute angle closure glaucoma in the left eye at the age of 51 years, with in¬ traocular tension measuring 58 mm Hg. A

peripheral iridectomy was performed, re¬ sulting in control of the intraocular pres¬ sure. Because the right eye also showed an extremely narrow anterior chamber angle

and moderate elevation of intraocular measuring 28 mm Hg, a similar procedure was done on this eye. However, the right eye required continued localized use of pilocarpine drops for control of ocu¬ lar tension. During the next few years, a cataract developed in the left eye, and when the patient was 55, the lens was re¬ moved. Removal was complicated by an iris prolapse, which required repair. One year later, the retina in the left eye be¬ came detached. Family history revealed that the pa¬ tient's brother had been highly hyperopic, but died of diphtheria at the age of 9 years. In addition, a paternal grandmother was alleged to have had "very poor vision." On examination, corrected vision was 20/200 in the right eye and hand move¬ ments at 0.6 meters (2 ft) in the left eye. The right eye showed no signs of inflam¬ mation, the cornea measured 7.25 mm in diameter, and a very narrow anterior chamber with a peripheral surgical colo¬ boma at 12 o'clock was noted. The trabecu¬ lar area could not be observed due to the bulging iris. Intraocular pressure mea¬ sured 14 mm Hg. The pupil was 1.5 mm in size, with posterior synechiae, and the lens showed moderate nuclear sclerosis. The fundus could not be visualized, but the vi¬ sual field was full, using the IV-2 test ob¬ ject of the Goldmann perimeter. The left eye showed a similar small cor¬ neal diameter and there was corneal opacification superiorly, where vitreous was pressure,

Fig 16.—Fluorescein angiogram of left eye of patient 5, 19 seconds after dye injection. Increased choroidal fluorescein apparent, due to decreased pigment in pigment epithe¬ lium. Narrow strips of retinal pigment epithelium are seen as dark defects. Fig 17.—Left eye of patient 4. Note extremely thick sclera, thickened choroid, and total retinal detachment without retinal breaks.

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Fig 18.—Enucleated left eye (patient 4) with anteroposterior axial length of 14 mm, equatorial diameter of 13.4 mm, and corneal diameter of 7.25 mm (low-power photo¬ micrograph) with 4-cm scale superimposed.

Fig 20.—Left eye of patient 4 showing thickened choroid infil¬ by mononuclear cells and hemorrhage, atrophie pigment epithelium, and retinal detachment. Atrophy of outer nuclear layer is evident; rods and cones are reduced in number (original magnification 105). trated

Fig 19—Left eye of patient 4 showing extremely thick structurally normal sclera (original magnification 55).

but

adherent to the corneal wound. A sector coloboma was present at 12 o'clock, but the anterior chamber angle was narrow. There were numerous peripheral anterior syn¬ echiae and the trabecular area could be visualized only in the area of the surgical coloboma. Ocular tension measured 7 mm Hg. No signs of intraocular inflammation were seen. The retina was totally detached with a choroidal elevation inferiorly (Fig 7). The disc could not be seen, due to the high ballooning retinal detachment. Since the retina was so highly elevated, and no retinal break could be found, drainage of the subretinal fluid was performed. During the operation, the horizontal diameter of the globe was found to mea¬ sure 13 mm. In addition, when sclerotomy for subretinal fluid drainage was at¬ tempted, it was found that the sclera mea¬ sured 2.5 mm in thickness. Following this procedure, the retina became much flatter, but the choroidal elevation persisted, being especially prominent nasally (Fig 8). Anal-

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ysis of the subretinal fluid removed during the operation failed to show any hyaluronic acid, indicating the absence of vitreous components in the subretinal fluid. This

additional evidence that the detach¬ was of the secondary

was

ment of the retina

type.

One week later, subretinal fluid began to reaccumulate and because of decreased transillumination in the choroidal eleva¬ tion nasally, the presence of an intraocu¬ lar tumor was suspected. Unfortunately, a radioactive phosphorus uptake test was not

performed. Ultrasonography

was

not

available for diagnostic evaluation in 1963. A complete medical evaluation failed to in¬ dicate any evidence of systemic malig¬ nancy, and the left eye was enucleated. During the past nine years, vision in the right eye decreased from 20/200 to hand movements at 0.6 meters (2 ft), apparently due to progression of cataractous opacities. Ocular tension has been kept below 20 mm Hg with acetazolamide. The patient has re¬ fused to have the cataract removed. This patient demonstrates high hyper¬ opia, acute angle closure glaucoma, and choroidal and secondary retinal detach¬ ment in an extremely small eye with a very thick sclera. Case 5.—A woman, an only child, +15 D hyperope, enjoyed central visual acuity of approximately 20/40 in each eye until the age of 57 years, when chronic glaucoma with very narrow anterior chamber angles was diagnosed. Intraocular pressure mea¬ sured 40 mm Hg in the right eye and 27 mm Hg in the left. Due to the failure of miotic therapy in controlling her intraocu¬ lar pressures, surgery was performed on each eye, consisting of a peripheral iridec¬ tomy with thermal cauterization of the wounds superiorly. Ocular tensions were normalized by these procedures. Six years later, vision had been reduced sufficiently by the development of cataracts to justify bilateral cataract extractions, which were done by the inferior route in order to avoid the filtering cicatrices. Six months after cataract surgery on the left eye, vision failed and a retinal detachment was diag¬ nosed. 3.

Fig 22.—Pedigree

of

D-1-O

í~

"1

patients 2

and

Fig 21 .—Left eye of patient 4 showing shallow anterior chamber side. Cornea is artifactually distorted at anterior pole of globe. On examination in 1969, vision measured 20/30 in the right eye with a +21 D sphere and 20/300 in the left eye with a +20 D sphere (aphakic correction). Family his¬ tory revealed no evidence of any impres¬ sive ocular disorder, such as glaucoma or retinal detachment. The right cornea was small, measuring 10 mm in horizontal diameter (Fig 9), and the anterior chamber angle was very narrow with many periph¬ eral anterior synechiae. Peripheral surgi¬ cal colobomas were seen at 12 o'clock and at 6 o'clock. There were no keratic precipi¬ tates, the aqueous was clear, and the ocu¬ lar tension measured 12 mm Hg. Fundus examination revealed a diffuse choroidal detachment extending from the posterior pole (Fig 10) to the extreme periphery, where a high annular choroidal elevation was noted (Fig 11). The left eye also showed a corneal diameter of 10 mm (Fig 12), a narrow ante¬ rior chamber angle, a peripheral surgical coloboma at 12 o'clock, and another at 4 o'clock. No signs of intraocular inflamma¬ tion were present. The ocular tension mea¬ sured 10 mm Hg. A prominent peripheral annular choroidal detachment, as well as a

Q

-Case 2

-m

closed

on

left

diffuse posterior choroidal elevation and a low, smooth retinal detachment, without retinal breaks, were observed in the fun¬ dus (Fig 13).

General medical evaluation was nonand laboratory studies failed to indicate any systemic disease. Analysis of the CSF showed no cells in the fluid and the total protein level was normal, 33 mg/100 ml. -scan ultrasonography re¬ vealed that the anteroposterior axial length of the right eye was 16.5 mm and the left was 17.0 mm (Fig 14). B-scan ul¬ trasonography of the left eye showed the extensive choroidal elevation, which was apparent clinically (Fig 15). The choroidal elevation was more marked anteriorly, ex¬ tending to the scleral spur. Posteriorly, there was a diffuse choroidal elevation. Bscan ultrasonography failed to show the very low retinal detachment distinct from the choroidal elevation, since separation between retina and choroid posteriorly was probably less than 1 mm. Fluorescein angiography of the left eye revealed normal filling of the retinal ves¬ sels. Increased choroidal fluorescence was noted at the posterior pole, due to de-

contributory

Fig 23—Pedigree of patient 4. One male sibling opic and the paternal grandmother had had "very

KEY

angle

of propositus poor vision."

was

extremely hyper-

KEY -Poor vision

-Case3

-

_Hyperopic

Died at age 8

-Case 4

m

s

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Fig 24.—Cross section of nanophthalmic eye with thick sclera, thickened choroid, and diffuse choroidal detachment, more marked peripherally.

Fig 25.—With further progression of pe¬ ripheral choroidal detachment, iris root is rotated so that filtration angle is ob¬ structed and glaucoma occurs.

creased pigment in the pigment epithe¬ lium. Narrow strips of retinal pigment epi¬ thelium remained intact and were seen as dark defects in front of the background of choroidal fluorescence (Fig 16). Prednisone was administered orally, 100 mg/day for one week, followed by a 100mg dose of prednisone every other day; within one month the retinal detachment had begun to subside. Vision improved to 20/70. Steroid therapy was then gradually reduced and finally terminated after one year, when vision had improved to 20/40 with correction. However, the peripheral annular choroidal detachments persisted in each eye. One year later, there was a re¬ currence of retinal detachment in the left eye, which once again responded to sys¬ temic steroid therapy. Patient 5 shows the association of high hyperopia, small ocular dimensions proved by ultrasonography, glaucoma with nar¬ row anterior chamber angles, choroidal ele¬ vation, and secondary retinal detachment.

the sclera. Neither eye showed choroi¬ dal elevation or retinal detachment. In contrast to O'Grady's patient, the left eye enucleated from patient 4 had been +13 D hyperopic and was considerably smaller in size. In addi¬ tion, choroidal elevation and retinal detachment were observed after sur¬ gery for glaucoma. The cut specimen showed the following: very thick sclera measuring 2.0 mm, thickened choroid, and retinal detachment with¬ out retinal breaks (Fig 17). A lowpower photomicrograph with a 4-cm scale indicated the anteroposterior axial length of the eye to be 14.0 mm, the equatorial diameter to be 13.4 mm, and the corneal diameter to be 7.25 mm (Fig 18). The sclera showed normal cellular and fibrillar structure. The scleral blood vessels showed no signs of scle¬ rosis or perivascular inflammation (Fig 19). The choroid, which was clini¬

PATHOLOGY In

1971, O'Grady described

a

23-

whose refractive error 7 D and OS + 8 D.13 Severe glaucoma occurred in each eye, re¬ quiring several surgical procedures. Both eyes ultimately became blind with absolute glaucoma, and enucleation was performed. Measurement of the globes revealed corneal diameters of 9 mm, and the transverse diame¬ ters of the globes to be 20 mm. No mention was made of the thickness of

year-old

was

OD

man

+

cally diagnosed as detached, was ex¬ tremely thick, measuring 2.0 mm in some sections, but was not separated

from the sclera by fluid or blood. In¬ stead, the choroid was very edema¬ tous, with the choroidal blood vessels engorged, and there was diffuse infil¬ tration of the choroid by mononuclear cells (Fig 20). Some sections showed choroidal hemorrhage, which resulted in the mistaken diagnosis of malig¬ nant melanoma. The pigment epithe-

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Fig 26.—Extensive secondary retinal de¬ glaucoma surgery. Note iri¬ dectomy performed on right side. tachment after

found to be absent in some generally atrophie. The de¬ tached retina showed atrophy of the outer nuclear layer, and the rods and cones were reduced in number and showed fragmentation and irregular¬ ity. The retinal vessels were sclerosed with round cells surrounding them. Cystoid degeneration was very marked in the peripheral retina. The subretinal space was occupied by an eosinophilic coagulum containing red blood cells and pigment-laden macro¬ Hum

was

areas, and

phages.

The anterior chamber was gener¬ ally narrow and was closed in many sections (Fig 21). Dense posterior synechiae were observed adherent to the lens capsule. The iris showed in¬ flammatory mononuclear cells near the pupillary margin. COMMENT

Analysis of the data presented in these five cases permits the desciption of a syndrome that has certain consis¬ tent characteristics (Table). The pa¬ tients were extremely hyperopic indi¬ viduals ( +13 to +18 D) of either sex who had useful central vision with correction and no other apparent ocu¬ lar anomalies. The first indication of serious ocular difficulty was glau¬ coma, which was usually acute. It was first diagnosed in the fourth to sixth decades of life and characterized by

anterior chamber all cases, choroidal eleva¬ tion and secondary retinal detach¬ ment were observed after glaucoma had been diagnosed and surgically treated. In no instance was a fundus abnormality observed prior to a sur¬

extremely angles. In

narrow

gical procedure. A familial predisposition is sug¬ gested, as two of the patients de¬ scribed (cases 2 and 3) are siblings, (Fig 22) and in one instance (case 4), a brother of the patient was known to have been extremely hyperopic prior to his death at the age of 9 years,

paternal grandmother had had vision" "poor (Fig 23). The other pa¬ tients described (cases 1 and 5) had no siblings, and adequate data regard¬ ing their parents' ocular status was and

a

not known.

Clinical observation of the globes involved revealed that the corneal diameter was small in all cases, mea¬ suring approximately 10 mm horizon¬ tally, while in case 4 it measured only 7.25 mm. In three of the patients, the diameter of the eye could be deter¬ mined. In case 1, measurements at surgery revealed the diameter to be 16 mm at the equator; in case 4, the equatorial diameter was found to be 13 mm; patient 4 was later studied histologically, the fixed specimen hav¬ ing an equatorial diameter of 13.4 mm. Patient 5 was studied by ultra¬ sonography, and the anteroposterior length of the two eyes was 16.5 and 17 mm. An unusually thick sclera (2.5 mm), which is apparently part of this syndrome, was observed in the two patients (cases 1 and 4) who under¬ went sclerotomy for drainage of sub¬ retinal fluid. In the other three cases, the scleral thickness could not be measured. With two exceptions, laboratory and general medical evaluation failed to provide any consistent findings that might be related to the ocular abnormalities. First, analysis of sub¬ retinal fluid from patients 1 and 4 failed to show hyaluronic acid. Since hyaluronic acid is a component of the vitreous, it is found in the subretinal fluid in cases of rhegmatogenous reti¬ nal detachment.101'- However, in the case of a secondary retinal detach¬ ment with no retinal break, hyaluron-

Summary of Case Histories Case

+13 +13 +18_+15 Hyperopia_+13 Sex_M_M F_M_F Glaucoma as initial problem_+_+_+_+_+_ at onset of

glaucoma,

Age

Narrow Choroidal Retinal

yr_31_51_43_51_57

angle_+_+_+_+_+ elevation_+_+_+_+_+ detachment_j-_j-_+_+_+ Familial_—_+_+_+_— Small corneal diameter +

diameter_16 mm

Small equatorial Thick CSF total protein,

+

+

+

+

?_?_13 mm_17 mm

sclera_+_?_?_+_ mg/100 ml_68_73 31_.^__33

CSFpleocytosis_0_0_0_.^._TJ ic acid cannot enter the subretinal space. Therefore, in the two cases in which this analysis was performed, the retinal detachment was proved to be of

a secondary type. Second, analysis of the CSF showed

elevated total protein levels but no pleocytosis in two of the four patients on whom this test was performed (cases 1 and 2). The presence of an el¬ evated CSF total protein level in pa¬ tients with choroidal elevation and secondary retinal detachment has previously been described. The condi¬ tion has been named uveal effusion.1" In contrast to Harada syndrome, pa¬ tients with uveal effusion do not ex¬ hibit alopecia, poliosis, vitíligo, dysacousia, or lymphocytosis in the CSF. However, the CSF total protein level is often elevated. Moreover, eyes af¬ flicted with uveal effusion fail to show any relevant signs of anterior seg¬ ment inflammation. In this series, none of the patients exhibited the hallmarks of Harada syndrome and in no case was there any significant sign of anterior ocular inflammation. Thus, it is apparent that these five patients show an unusual type of uveal effusion that occurs in highly hyperopic, small eyes and becomes evident only after the patient has been operated on for glaucoma ac¬

companied by extremely

narrow an¬

terior chamber angles. The importance of recognizing this condition is emphasized by case 4, since choroidal elevation was mistak¬

enly diagnosed

as a

possible malig¬

nant melanoma and enucleation of

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the eye was performed. The diagnosis of malignant melanoma was corrobo¬ rated by the localized decrease in transillumination. However, histo¬ logie examination subsequently re¬ vealed that the reduced transmission of light through the choroidal eleva¬ tion was probably the result of hem¬ orrhage, that occurred after drainage of subretinal fluid. Although a radio¬ active phosphorus (:1-P) uptake test was not performed in case 4, it is un¬ likely that such a procedure would have been helpful. The !2P tests per¬ formed on three patients with uveal effusion showed a marked increase in uptake (100% to 300%) over the areas of choroidal elevation 48 hours after injection of radioactive phosphorus (R. J. Brockhurst, unpublished data). Thus, a false positive ,2P test may oc¬ cur in uveal effusion without the pres¬ ence of a malignant tumor. Another important reason for the recognition of this syndrome is dem¬ onstrated by case 2. In the left eye, which developed a retinal detachment after glaucoma surgery, a conven¬ tional retinal detachment operation failed. It has already been reported that retinal detachment surgery usu¬ ally is followed by complete loss of vi¬ sion in cases of uveal effusion.1" Finally, since retinal detachment did not occur until after surgery for glaucoma, it would appear advisable to exhaust all medical measures for the control of glaucoma before re¬ sorting to surgery on eyes with nanophthalmia. The most beneficial treatment of nanophthalmic eyes ex-

hibiting secondary retinal detach¬

of sys¬ temic steroids. In four of the five patients described (cases 1 through 3, and 5), such therapy resulted in par¬ tial reattachment of the retina with visual improvement. The best results are obtained with relatively high dos¬ ages. Unfortunately, however, such treatment is only palliative and it is apparent that relapses often occur, requiring repetition of the therapeu¬ tic regimen. Moreover, it is obvious from the results of case 1 that steroid therapy may be beneficial at one time, but fail during a later relapse. The response of choroidal elevation to steroid therapy is usually not com¬ plete. In cases 3 and 5, although the retinal detachment responded to steroid therapy, the choroidal eleva¬ tion persisted, although to a lesser de¬ ment appears to be the

use

gree.

The mechanisms responsible for this syndrome are not apparent from the data of these five cases. The clini-

cal findings and the course of the disorder do not seem to imply an in¬ flammatory basis. Instead, some ge¬ netic predisposition seems to result in a failure of the eye to grow to proper dimensions, the anterior chamber being very narrow. Uveal effusion characterized by diffuse choroidal de¬ tachment, especially in the periphery, may then occur (Fig 24). As choroidal elevation becomes more marked, the iris root rotates so that the filtration angle is obstructed and glaucoma oc¬ curs (Fig 25). Following surgery for glaucoma, extensive secondary reti¬ nal detachment occurs (Fig 26). Un¬ fortunately, in these five cases the ex¬ treme fundus periphery was not carefully examined prior to the onset of glaucoma. The occurrence of glau¬ coma in the fourth to sixth decades of life would seem to indicate that the developmentally narrow angle has fi¬ nally been embarrassed, probably by an unrecognized peripheral chroidal elevation, and glaucoma ensues, re-

quiring surgical therapy. Following

this traumatic insult to the eye, an imbalance in the dynamics of the cir¬ culatory system of the globe appears to occur, with additional thickening of the choroid and accumulation of subretinal fluid. Analysis of subreti¬ nal fluid from a case of uveal effu¬ sion14 revealed that this fluid contains an unusually large amount of albu¬ min (27.5 gm/100 ml), one acid

phosphatase isoenzyme normally found in plasma, and no inflamma¬ tory cells. This indicates

an

abnormal

permeability of the Lamina choroidocapillaris to the smaller protein molecules of plasma and the absence of an inflammatory basis for uveal ef¬ fusion. Why such a situation should exist in small hyperopic eyes is yet to be explained. This paper was accepted as a thesis in partial fulfillment of the requirements for membership in the American Ophthalmological Society.

References 1. Black M: Twins with high hyperopia. Am J Ophthalmol 7:375-376, 1924. 2. Southgate PT: High hypermetropia. Am J Ophthalmol 33:466-467, 1950. 3. Witmer R: Hohe Hypermetropie und Ablatio. Ophthalmologica 121:178-179, 1951. 4. Hatcher WF: Extreme axial hyperopia. Arch Ophthalmol 48:161-162, 1952. 5. Manning EL: Severe hyperopia. Am J Ophthalmol 36:983, 1953. 6. Rathsch\l=u"\ler R, Dufour R: Pathologie de l'hyperm\l=e'\tropieforte: P\l=e'\riphl\l=e'\biteet d\l=e'\collement de la r\l=e'\tine,Ophthalmologica 129:327-330,

1955. 7. Vetter J: Ablatio retinae als Zweiterkr\l=a"\nkung bei Mikrophthalmus und Glaukom. Klin Monatsbl f Augenh 134:421-426, 1959. 8. Zuccoli A: Neuer Beitrag zum Bild der Mak-

rozysten bei der hohen Hypermetropie. Ophthalmologica 145:419-424, 1963. 9. Duke-Elder S: System of Ophthalmology. St. Louis, Mo, CV Mosby Co, 1963, vol 3, pp 488-495. 10. Schepens CL, Brockhurst RJ: Uveal effu-

sion: I. Clinical picture. Arch Ophthalmol 70:189\x=req-\ 201, 1963. 11. Godtfredsen E: Investigations into hya-

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luronic acid and hyaluronidase in the subretinal fluid in retinal detachment, partly due to ruptures and partly secondary to malignant choroidal melanoma. Br J Ophthalmol 33:721-732,1949. 12. Sweeney B, in discussion, Schepens CL and Regan CDJ (eds): Controversial Aspects of the Management of Retinal Detachment. Boston, Little Brown & Co, 1965, pp 315-316. 13. O'Grady RB: Nanophthalmos. Am J Ophthalmol 71:1251-1253, 1971. 14. Brockhurst RJ, Lam KW: Uveal effusion: II. Case report with analysis of subretinal fluid. Arch Ophthalmol 90:399-401, 1973.