NANOPHTHALMOS WITHUVEAL EFFUSION:

A NEW CLINICAL ENTITY*

BY Robert J. Brockhurst, MD

IN CQNTRAST TO HIGH MYOPIA, HIGH DEGREES OF HYPEROPIA HAVE RECEIVED L1T-tle attention in the ophthalmic literature. In 192£1, Black' described twinsisters, aged 28 years, who showed hyperopia of approximately sevendiopters in both eyes. In 1950, Southgate2 described two children, aged 6and 12 years, whose hyperopic errors were 15 diopters and 17 dioptersrespectively. Neither Black nor Southgate noted any other abnormalitiesor ocular disorders such as microphthalmos, glaucoma, or retinal detach-ment. In 1951 Witmer3 first reported the association of retinal detach-ment with high degrees of hyperopia. In two of his patients, he observedhyperopic errors of 12 to 15 diopters. The retinal detachments werecharacterized by a yellowish discoloration ofthe retina and in neither casewas he able to demonstrate a retinal break. Surgery failed to reattach thedetached retinas.

In 1952, Hatcher4 reported the case ofa young girl, aged 9 years, with arefractive error of +21 diopters in the right eye and +20 diopters in theleft eye. Glaucoma was present in each eye. The corneal diameters were10 mm; 11.75 mm being considered normal for her age. Manning5 in 1953reported the association ofhigh hyperopia with corneal vascularization. Inhis report he quoted Braley as having observed a case of high hyperopiawhich later developed a "solid" retinal detachment. This suggests that theretinal elevation may have been accompanied by or was due to a choroidaldetachment.

Rathschuler and Dufour6 reported three cases of high hyperopia as-sociated with fundus problems in 1955. In one patient, whose refractiveerror was +14 diopters in both eyes, there was an apparently idiopathicretinal detachment in one eye. The other two patients, both ofwhom hadhistories of pulmonary disease, showed hyperopia of +8 and +10 diop-

*From the Department of Retina Research, Retina Foundation and the Retina Associates,100 Charles River Plaza, Boston, Massachusetts.TR. AM. OPHTH. Soc., vol. LXXII, 1974

ters, as well as evidence of periphlebitis, retinitis proliferans, and vitre-ous hemorrhage. There is a distinct possibility that these cases may havebeen examples of Eales' disease occurring in hyperopic eyes.

In 1959, Vetter7 reported on the association of microphthalmos,glaucoma, and retinal detachment. His report included four cases ofchronic glaucoma with retinal detachment and one case of microphthal-mos with retinal detachment. Apparently the retinal detachments wererheginatogenous in nature, as retinal breaks were found. Unfortunately,the refractive error of the microphthalmic patient was not recorded. Ofthe other four patients with glaucoma, two were emmetropic and twowere myopic.

In 1963, Zuccoli8 reported two cases of hyperopia (+6 and +10 diop-ters) occurring in men and associated with cysts of the temporal retina.However, his patients did not have retinal detachment or glaucoma andthe fundus picture suggests the possibility of retinoschisis.

Microphthalmos is a general term which includes a wide variety ofdisorders sharing one common finding - an eye smaller than normal.Many microphthalmic patients characteristically show other developmen-tal anomalies of the eye or body. For example, microphthalmos may bevery severe, resulting in such a small, disorganized eye that no ocularstructure is visible - anophthalmos. In other cases, it is frequentlycomplicated by developmental defects of the fetal fissure and coloboma ofthe iris, choroid, and retina is present. Sometimes it is associated withdental, skeletal, cardiovascular, and urogenital developmental defects.

In contrast to the forms of microphthalmos which are associated withother ocular or systemic developmental abnormalities, there is a pureform of microphthalmos which has been referred to as nanophthalmos(Greek nanos, dwarf).9 In pure microphthalmos, or nanophthalmos, theeye is small in its overall dimensions but is not affected by other grossdevelopmental defects nor accompanied by other systemic developmen-tal defects. The nanophthalmic eye is typically reduced in volume withoutother apparent abnormality. The palpebral fissure is narrow and the eyeappears deeply set in the orbit. Marked hypermetropia exists in thevicinity of +18 diopters. The eyeball diameter varies from 14 to 17 mmand glaucoma is frequently present. The predisposition to glaucomaapparently results from the presence of a relatively normal-sized lenswhich embarrasses the filtration meshwork. Both dominant and recessiveforms of heredity in nanophthalmos have been described.The constant association of several apparently unrelated abnormalities

suggests a common denominator or syndrome. This report describes five

372 Brockhurst

patients who demonstrate a hitherto unreported clinical syndromecharacterized by the association of pure microphthalmos, or nanophthal-mos, and uveal effusion.10 The features demonstrated include small eyeswith thick sclera, high degrees ofhypermetropia, glaucoma, and choroid-al elevation with retinal detachment of the secondary (non-rhegmato-genous) type.

CASE REPORTS

CASE 1A white male, an only child with +13 diopters hypermetropia, first developedacute angle closure glaucoma in the left eye at age 31. The family eye history wasnot significant. Following surgery for glaucoma, the left eye developed malignantglaucoma and became blind. At the age of 47, acute angle closure glaucomaoccurred in the right eye. The intraocular pressure was 65 mm Hg and thefiltration angle was closed. A sector iridectomy and lens extraction were per-formed. Two days after this procedure, an annular, peripheral choroidal detach-ment and temporal retinal detachment extending into the macula were observed.No retinal break could be demonstrated. Three months later, the choroidaldetachment was considerably smaller, but the retina remained detached in thetemporal periphery, extending slightly posterior to the equator. Two years later in1957 central vision failed in the right eye.The corrected vision was limited to hand movements at 2 feet in the right eye

with a correction of +21 diopters (aphakic). The intraocular pressure was 20 mmHg. The cornea measured 10.5 mm in diameter horizontally. A sector colobomawas observed at the 12 o'clock position and gonioscopy revealed the angle to bevery narrow with many peripheral synechiae. No keratic precipitates, aqueousflare, or cells were seen. The retina was totally detached, the fluid shifting to adependent position, and showing smooth high balloons without any evidence of aretinal break (Figure 1). There was a diffuse annular choroidal detachment in theperiphery. Ocular tonography revealed a coefficient of outflow of 0.05 in the righteye.The left eye was blind, with an ocular tension which measured 70 mm Hg.

Corneal edema was present, the anterior chamber appeared flat, and the anglewas closed. A moderate flare was present in the aqueous humor and a sectorcoloboma was present superiorly, the pillars of the iris being adherent to theposterior surface of the cornea. Corneal vascularization was noted superiorly inthe region of the coloboma. A mature cataract precluded examination of thefundus. His general physical condition was within normal limits, as were theresults of laboratory studies for uveitis. Examination of the cerebrospinal fluid,however, revealed an elevated total protein of 68 mg percent but no cells werefound. The upper limit of normal protein is 45 mg percent.

Nanophthalmos 373

Brockhurst

FIGURE 1Fundus drawing of the right eye of Case 1, showing total secondary retinal detachment

without breaks and peripherl annular choroidal detachment.

Subretinal fluid was drained and an encircling polyethylene tube (# 90) wasplaced around the right globe to restore intraocular pressure. Following surgerythe retina became partially reattached but no retinal breaks could be discovered.During surgery, the diameter of the globe was found to measure 16 mm and thesclera measured 2.5 mm in thickness at the site of the sclerotomy just posterior tothe equator. Analysis of the subretinal fluid which was drained at operation,revealed the absence of hyaluronic acid. Such a finding indicates that no fluidvitreous is present in the subretinal fluid and is almost certain evidence that noretinal break exists. 10,11,12The clinical diagnosis of secondary retinal detachment was thus confirmed and

the patient was treated with prednisone. The dosage was 40 mg per day for onemonth and then was reduced to 30 mg per day. After two months of treatment,

374

Nanophthalmos

FIGURE 2Right fundus ofCase 1 two months after systemic steroid treatment. Note that the subretinalfluid has been absorbed, except for that located temporal to the macula. The choroidal

detachment, however, persisted.

the retina became reattached, except for a residual area temporal to the macula.However, the choroidal detachment persisted (Figure 2). Prednisone was re-duced to 20 mg per day; two months later the retinal detachment lessened,involving only the temporal periphery. Vision, which had been limited t9 handmovements at one foot, improved to 20/300. During the next ten years, thetemporal detachment occasionally increased in extent but responded to periodiccourses of systemic steroids. In every way this retinal detachment resembled thatobserved in uveal effusion.10 In 1969, when the patient was 61 years of age, theretinal detachment became more extensive, invaded the macula and vision was

375

Brockhurst

FIGURE 3Photograph of polyethylene 90 tubing which had been used as an equatorial encirclingelement in the right eye of Case 1. The length of the encircling element measured 47 mm,

indicating the diameter of the globe as approximately 15 mm.

reduced to hand movements once again. Since the detachment proved to berefractory to systemic steroids, a second subretinal fluid drainage was performed.The encircling tube which had been inserted 14 years previously was removed. Itscircumference was 47 mm, indicating a diameter of the globe of 15 mm (Figure 3).Fluid gradually returned and another subretinal fluid drainage was performed sixmonths later. Since that time, a peripheral secondary retinal detachment haspersisted in spite of systemic steroid therapy. Although the intraocular pressurehas been well controlled with acetazolamide and local medication, the-visual fieldhas gradually become limited to a small temporal island of vision 10 degrees indiameter.The 'important features illustrated by this case are high hypermetropia, small

cornea size, small ocular dimensions with a very thick sclera, glaucoma withnarrow filtration angle, choroidal detachment, and secondary retinal detachment.The cerebrospinal fluid showed no lymphocytosis, but the total protein waselevated. It appears that the choroidal elevation and retinal detachment representuveal effusion'0 occurring in an extremely small hyperopic eye which had de-veloped glaucoma as its first serious ocular problem.

376

CASE 2

A white male, a high hyperope measuring OD +13.75 S-2.00 cx 1800 and OS+14.50 S-2.00 cx 1800, suddenly developed acute angle closure glaucoma in hisright eye at the age of 51 years. The intraocular tension was 55 mm Hg. There wasno family history of any genetic, ocular, or systemic disorder at this time. Theacute attack of glaucoma in the right eye was treated surgically by a sectoriridectomy. Because the left eye showed an extremely narrow angle and a slightelevation of intraocular pressure measuring 28 mm Hg, a peripheral iridectomywas done. Two years later, an inferior retinal detachment occurred in the left eyewhich failed to reattach after retinal surgery. A few months later, a retinaldetachment also occurred in the right eye.

FIGURE 4Fundus drawing of the right eye of Case 2, demonstrating an inferior secondary retinaldetachment with intraretinal exudates. Choroidal detachment was present in the upper

nasal and upper temporal quadrants.

Nanophthalmos 377

In 1960, the corrected vision measured 20/200 in the right eye and bare lightperception in the left eye. The right eye showed a corneal diameter of 10 mm,early band keratopathy, a very shallow anterior chamber angle with manyperipheral anterior synechiae, elevated intraocular pressure of 32 mm Hg, asector coloboma at 12 o'clock, and early peripheral cortical lens opacities. The eyeappeared white and was free of signs of inflammation. The vitreous was clear andshowed no inflammatory cells. An inferior, secondary type, retinal detachmentwith many intraretinal exudates, but with no observable retinal breaks, waspresent. Choroidal detachment was also observed in the upper temporal andupper nasal quadrants (Figure 4).The left eye showed a corneal diameter of 10 mm, intraocular pressure of 6 mm

Hg, folds in Descemet's membrane, early band keratopathy, a narrow anglewhich was completely closed, a small peripheral surgical coloboma at the 12o'clock position, marked iris atrophy, seclusio pupillae and an immature cataract.A slight flare without cells was present in the aqueous humor. The fundus couldnot be visualized, even with indirect ophthalmoscopy.The retinal detachment in the right eye was considered not to be rhegmatogen-

ous, and an extensive medical and conventional uveitis workup was performed.All studies were negative with the exception of the cerebrospinal fluid studieswhich showed an elevated total protein of 73 mg percent without lymphocytosis.Serum electrophoresis was normal. The patient was treated with oral prednisone,125 mg per day in a single dose for three days, which was then reduced to 100 mgper day for one week, and then to 100 mg every other day. Two weeks after theonset of therapy, vision had improved to 20/70 and the retinal detachment hadbegun to subside. One month later, the retina was almost completely reattachedand prednisone was reduced to 75 mg every other day. Control of intraocularpressure was not satisfactory, in spite of oral acetazolamide and the instillation oflocal pilocarpine drops. At this time, the patient returned home (abroad). Onemonth later, he suddenly expired, the exact cause of death not being determined.Unfortunately, postmortem examination and histological studies of the eyes werenot performed.

This case demonstrates high hypermetropia associated with angle closureglaucoma, choroidal detachment, secondary retinal detachment and an elevatedtotal protein in the cerebrospinal fluid. As in the first case, Case 2 demonstratesthe association of uveal effusion with high hypermetropia, angle closure glaucomabeing the first symptom of this serious ocular disease.

CASE 3

In 1965 a white female, aged 43, sister of the abovs patient (Case 2), +13Dhypermetropia, developed acute angle closure glauc-oma in the left eye. Theocular tension measured 65 mm Hg. After eight months of miotic therapy, thetension remained elevated at 30 mm Hg; therefore, trephination was performed.One week after this procedure the retina detached. A review of the family historyrevealed that only the patient and her brother (Case 2) were hypermetropic.

378 Brockhurst

There was no history of other members of the family suffering any significantocular disorder. General medical evaluation and uveitis survey were not remark-able. Cerebrospinal fluid examination revealed a normal total protein of 31 mgpercent and the absence of any cells.The corrected vision was 20/30 in the right eye and hand movements at 4 feet in

the left eye. The right eye showed no signs of inflammation, a clear corneameasuring 10mm in diameter, a very narrow angle in which the trabeculum couldnot be observed, ocular tension of 9 mm Hg, a clear lens, and peripheral choroidaldetachment (Figure 5). Visual field examination showed no defect in the right eye(Goldmann IV-2 test object).

FIGURE 5Fundus drawing of the right eye of Case 3 showing peripheral annular choroidal

detachment.

Nanophthalmos 379

The left eye showed a small cornea, measuring 10 mm, a peripheral surgicalcoloboma at the 12 o'clock position with a filtering cicatrix, ocular tension of 10mm Hg, and a very shallow anterior chamber, although the trabecular area couldbe seen. A slight flare without cells was present in the aqueous humor. Peripheralsynechiae were noted near the iridectomy and many posterior synechiae werepresent, resulting in a small bound down pupil. The lens was clear and fundusexamination showed a total retinal detachment. Since ophthalmoscopy was dif-ficult due to the miotic pupil and no retinal break could be found, a sectoriridectomy was performed. Following this procedure, the fundus could be betterevaluated and a peripheral choroidal detachment, as well as a secondary typeretinal detachment without breaks, was diagnosed (Figure 6). The patient was

FIGURE 6Fundus drawing of the left eye of Case 3. Secondary retinal detachment and peripheral

choroidal detachment are evident.

Brockhurst380

treated with oral prednisone - 40 mg per day for two months and was thenreduced to 10 mg per day. After four months, the retina became reattached.Vision improved to 20/400. The peripheral choroidal detachment persisted inboth eyes.

Case 3 demonstrates the association of high hypermetropia, angle closureglaucoma, choroidal detachment and secondary retinal detachment which re-sponded to steroid therapy. In addition, a familial predisposition to this unusualproblem is evident in Cases 2 and 3.

CASE 4

A white male, +18 diopters hyperopic, developed acute angle closure glaucomain the left eye at the age of 51. The intraocular tension measured 58 mm Hg. Aperipheral iridectomy was performed and resulted in control of the intraocularpressure. Because the fellow right eye also showed an extremely narrow anteriorchamber angle and moderate elevation of intraocular pressure, measuring 28 mmHg, a similar procedure was done on this eye. However, the right eye requiredcontinued use of local pilocarpine drops for control of ocular tension. During thenext few years, a cataract developed in the left eye, and when the patient was 55,the lens was removed. Removal was complicated by an iris prolapse whichrequired repair. One year later, the retina in the left eye became detached.Family history revealed that the patient's brother had been highly hyperopic,

but died of diphtheria at the age of nine years. In addition a paternal grandmotherwas alleged to have had "very poor vision". Upon examination, corrected visionwas 20/200 in the right eye and hand movements at 2 feet in the left eye. The righteye showed no signs of inflammation, the cornea measured 7.25 mm in diameter,and a very narrow anterior chamber with a peripheral surgical coloboma at 12o'clock was noted. The trabecular area could not be observed due to the bulgingiris. Intraocular pressure measured 14 mm Hg. The pupil was 1.5 mm and therewere posterior synechiae. The lens showed moderate nuclear sclerosis. Thefundus could not be visualized, but the visual field was full, using the IV-2 testobject of the Goldmann perimeter.The left eye showed a similar small corneal diameter and there was corneal

opacification superiorly, where vitreous was adherent to the corneal wound. Asector coloboma was present at the 12 o'clock position, but the anterior chamberangle was narrow. There were numerous peripheral anterior synechiae and thetrabecular area could be visualized only in the area of the surgical coloboma.Ocular tension measured 7 mm Hg. No signs of intraocular inflammation wereseen. The retina was totally detached with a choroidal elevation inferiorly (Figure7). 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

measure 13 mm. In addition, when sclerotomy for subretinal fluid drainage wasattempted, it was found that the sclera measured 2.5 mm in thickness. Following

Nanophthalmos 381

Brockhurst

FIGURE 7Fundus drawing of left eye of Case 4. A total secondary retinal detachment was present and

in addition, choroidal detachment was noted inferiorly under the detached retina.

the operation, the retina became much flatter but the choroidal elevation per-sisted, being especially prominent nasally (Figure 8). Analysis of the subretinalfluid removed during the operation failed to show any hyaluronic acid, indicatingthe absence of vitreous components in the subretinal fluid. This was additionalevidence that the detachment of the retina was of the secondary type.One week later, subretinal fluid began to accumulate again and because of

decreased transillumination in the choroidal elevation nasally, the presence of anintraocular tumor was suspected. Unfortunately, a radioactive phosphorus uptaketest was not performed. Ultrasonography was not available for diagnostic evalua-tion at this time (1963). A complete medical evaluation failed to indicate any

382

Nanophthalmos

FIGURE 8Left fundus of Case 4 after drainage of most of the subretinal fluid. Incarceration of theretina occurred at the drainage site at the four o'clock position. The choroidal elevation was

then better visualized. It was especially prominent nasally.

evidence of systemic malignancy and the left eye was enucleated. The histologicfindings are described later. During the past nine years, vision in the right eye hasdecreased from 20/200 to hand movements at 2 feet apparently due to progressionof a cataract. Ocular tension has been kept below 20 mm Hg with acetazolamide.The patient has refused to have the cataract removed.

This case demonstrates high hypermetropia, acute angle closure glaucoma, andchoroidal and secondary retinal detachment in an extremely small eye with a verythick sclera.

383

CASE 5

A white female, an only child, + 15 diopters hyperopic, had a central visual acuityof approximately 20/40 in each eye until the age of 57 years, when chronicglaucoma with very narrow anterior chamber angles was diagnosed. Intraocularpressure measured 40 mm Hg in the right eye and 27 mm Hg in the left eye. Dueto the failure of miotic therapy in controlling her intraocular pressures, surgerywas performed on each eye. The surgery consisted of a peripheral iridectomy withthermal cauterization of the wounds superiorly. Ocular tensions were normalizedby these procedures. Six years later, vision had been reduced sufficiently by thedevelopment of cataracts to justify bilateral cataract extractions which were doneby the inferior route in order to avoid the filtering cicatrices. Six months aftercataract surgery on the left eye, vision failed and a retinal detachment wasdiagnosed.Upon examination in 1969, vision measured 20/30 in the right eye with a +21

sphere and 20/300 in the left eye with a +20 sphere (aphakic correction). Familyhistory revealed no evidence of significant ocular disorder such as glaucoma orretinal detachment. The right cornea was small, measuring 10 mm in horizontaldiameter (Figure 9), and the anterior chamber angle was very narrow with manyperipheral anterior synechiae. Peripheral surgical colobomas were seen at the 12

FIGURE 9Photograph of the right eye of Case 5. Note absence of inflammatory signs, the eye beingcompletely white. An additional surgical coloboma is present at the 6 o'clock position,performed at the time ofcataract extraction by the inferior route. The corneal diameter is 10

mm. The eye sits deeply in the orbit.

384 Brockhurst

Nanophthalmos

FIGURE 10Stereo photograph of the right fundus of Case 5, demonstrating the marked elevation of the

choroid posteriorly, especially nasal to the disc.

o'clock and 6 o'clock positions. There were no keratic precipitates, the aqueouswas clear and the ocular tension measured 12 mm Hg. Ophthalmoscopic examina-tion revealed a diffuse choroidal detachment extending from the posterior pole(Figure 10) to the extreme periphery, where a high annular choroidal elevationwas noted (Figure 11).The left eye also showed a corneal diameter of 10 mm (Figure 12), a narrow

anterior chamber angle, a peripheral surgical coloboma at the 12 o'clock positionand another at the 4 o'clock position. No signs of intraocular inflammation werepresent. The ocular tension measured 10 mm Hg. A prominent peripheral annu-lar choroidal detachment, as well as a diffuse posterior choroidal elevation and alow, smooth retinal detachment, without retinal breaks, were observed in thefundus (Figure 13).

General medical evaluation was noncontributory and laboratory studies failedto indicate any systemic disease. Analysis of the cerebrospinal fluid showed nocells in the fluid and the total protein was normal (33 mg percent). A-scanultrasonography revealed that the anteroposterior axial length ofthe right eye was16.5 mm and the left was 17.0 mm (Figure 14). B-scan ultrasonography of the left

385

Brockhurst

FIGURE 11Fundus drawing of the right eye of Case 5. Note that the choroidal detachment was much

more elevated in the periphery.

eye showed the extensive choroidal elevation which was apparent clinically (Fi-gure 15). It is noteworthy that the choroidal elevation was more marked anterior-ly, extending to the scleral spur. Posteriorly there was a diffuse choroidal eleva-tion. B-scan ultrasonography failed to show the very low retinal detachmentdistinct from the choroidal elevation, since separation between retina and choroidposteriorly was probably less than 1 mm.

Fluorescein angiography of the left eye revealed normal filling of the retinalvessels. Increased choroidal fluorescence was noted at the posterior pole, due todecreased pigment in the pigment epithelium. Narrow strips of retinal pigmentepithelium remained intact and were seen as dark defects in front of thebackground of choroidal fluorescence (Figure 16).

386

Nanophthalmos

INp

1 'i :*?_I_1_

umuI,u IN I

FIGURE 12Photograph of anterior segment of left eye of Case 5. The eye is white and free of

inflammatoxy signs; the comeal diameter is 10 mm.

The patient was placed on prednisone, 100 mg per day orally for one weekfollowed by 100 mg prednisone every other day, and within one month the retinaldetachment began to subside. Vision improved to 20/70. Steroid therapy was thengradually reduced and finally terminated after one year, when vision had im-proved to 20/40 with correction. However, the peripheral annular choroidaldetachments persisted in each eye. One year later, there was a recurrence ofretinal detachment in the left eye, which once again responded to systemic steroidtherapy.Case 5 demonstrates the association of high hypermetropia, small ocular di-

mensions proven by ultrasonography, glaucoma with narrow anterior chamberangles, choroidal elevation, and secondary retinal detachment.

387

Brockhurst

FIGURE 13Left fundus of Case 5 revealing a diffuse choroidal detachment markedly elevated in the

periphery in all quadrants. In addition, a smooth flat retinal detachment is present.

388

Nanophthalmos

_ A A AAA"A" SL"I-* ------

4 4w zz _

0u

FIGURE 14A-scan ultrasonography of the eyes of Case 5. In the right eye and the left eye, the

anteroposterior axial length is shown to be 16.5 mm and 17.0 mm, respectively.

1B Cornea

I

Sciera

fat

FIGURE 15B-scan ultrasonography of the left eye of Case 5. Note the generalized elevation of thechoroid throughout the fundus, becoming more marked near the equatorial region and in

the area of the pars plana.

389

Brockhurst

FIGURE 16Fluorescein angiogram of the left eye of Case 5, 19 seconds after dye injection. Increasedchoroidal fluorescein is apparent, due to decreased pigment in the pigment epithelium.

Narrow strips of retinal pigment epithelium are seen as dark defects.

PATHOLOGY

In 1971, O'Grady described a 23-year-old male patient whose refractiveerror was +7 diopters in the right eye and +8 diopters in the left eye.13Severe glaucoma occurred in each eye, requiring several surgical proce-dures. Both eyes ultimately became blind with absolute glaucoma andenucleations were performed. The corneal diameters were 9 mm, and thetransverse diameters of the globes were 20 mm. No mention was made ofthe thickness of the sclera. Neither eye showed choroidal elevation orretinal detachment.

In contrast to O'Grady's case, the left eye enucleated from Case 4 ofthis series was + 13 diopters hypermetropic and was considerably smallerin size. In addition, choroidal elevation and retinal detachment wereobserved after surgery for glaucoma. The cut specimen showed thefollowing salient features: very thick sclera measuring 2.0 mm, thickenedchoroid, and retinal detachment without retinal breaks (Figure 17). A low

390

Nanophthalmos

-V_17FIGURE 17

Photograph of cut specimen of the left eye of Case 4. Note the extremely thick sclera,thickened choroid, and total retinal detachment without retinal breaks.

power photomicrograph with a 5 mm scale indicated the anteroposterioraxial length of the eye to be 14.0 mm, the equatorial diameter to be 13.4mm and the corneal diameter to be 7.25 mm (Figure 18).The sclera showed normal cellular and fibrillar structure. The scleral

blood vessels showed no signs of sclerosis or perivascular inflammation(Figure 19). The choroid, which was clinically diagnosed as detached, wasextremely thick measuring 2.0 mm in some sections but was not sepa-rated from the sclera by fluid or blood. Instead, the choroid was veryedematous. The choroidal blood vessels were engorged and there wasdiffuse infiltration of the choroid by mononuclear cells (Figure 20). Somesections showed choroidal hemorrhage which resulted in the mistakendiagnosis of malignant melanoma. The pigment epithelium was found tobe absent in some areas and generally atrophic. The detached retinashowed atrophy of the outer nuclear layer. The rods and cones werereduced in number and showed fragmentation and irregularity. Theretinal vessels were sclerosed with round cells surrounding them. Cystoid

391

Brockhurst

FIGURE 18Low-power photomicrograph with 5 mm scale superimposed, indicating small dimensions of

the left eye removed from Case 4.

degeneration was very marked in the peripheral retina. The subretinalspace was occupied by an eosinophilic coagulum containing red bloodcells and pigment laden macrophages.The anterior chamber was generally narrow and closed in many sec-

tions (Figure 21). Dense posterior synechiae were observed adherent tothe lens capsule. The iris showed inflammatory mononuclear cells nearthe pupillary margin.

392

Nanophthalmos

BBx

FIGURE 19Photomicrograph of left eye of Case 4, showing extremely thick but structurally

normal sclera.

393

Brockhurst

1OBx

FIGURE 20Photomicrograph of left eye of Case 4, showing thickened choroid infiltrated bymononuclear cells and hemorrhage, atrophic pigment epithelium, and retinaldetachment. Atrophy of the outer nuclear layer is evident; rods and cones are

reduced in number.

394

Nanophthalmos

FIGURE 21Photomicrograph ofleft eye ofCase 4, showing shallow anterior chamber angle closed on the

left side. The cornea is artefactually distorted at the anterior pole of the globe.

DISCUSSION

Analysis of the data presented in these five cases permits the descriptionof a syndrome which has certain consistent characteristics (Table 1). Thepatients were extremely hyperopic individuals (+13 to +18 diopters) ofeither sex who had useful central vision with correction and no otherapparent ocular anomalies. The first indication of serious ocular difficultywas glaucoma, which was usually acute. It was first diagnosed in thefourth to sixth decade of life and characterized by extremely narrowanterior chamber angles. In all of the patients, choroidal elevation andsecondary retinal detachment were observed after glaucoma had beendiagnosed and surgically treated. In no instance was a fundus abnormalityobserved prior to a surgical procedure. A familial predisposition issuggested, as two of the patients (Cases 2 and 3) are siblings (Figure 22).In one instance, (Case 4) a brother of the patient was known to have beenextremely hyperopic prior to his death at the age of nine years and apaternal grandmother had had "poor vision" (Figure 23). The otherpatients described (Cases 1 and 5) had no siblings and adequate dataregarding their parents' ocular status was not known.

395

TABLE 1. SUMMARY OF CASE HISTORIES

Case 1 Case 2 Case 3 Case 4 Case 5Hyperopia +13 +13 +13 +18 +15Sex M M F M FGlaucoma as initial problem + + + + +Age at onset of glaucoma 31 51 43 51 57Narrow angle + + + + +Choroidal elevation + + + + +Retinal Detachment + + + + +Familial - + + +Small Corneal diameter + + + + +Small equatorial diameter 16 mm ? 13 mm 17 mmThick sclera + ? ? + ?CSF total protein 68 mg% 73 mg% 31 mg% ? 33 mg%CSF pleocytosis 0 0 0 0

I KEY*-Cose2

* -CC7se 3

FIGURE 22Pedigree of Cases 2 and 3

23I KEY

- Poor vision

//yperopicDied at oge8

U-Case 4N

FIGURE 23Pedigree of Case 4. One male sibling of propositus was extremely hyperopic and the

paternal grandmother had had "very poor vision".

396 Brockhurst

Clinical observation of the globes showed that the corneal diameter wassmall in all patients, measuring approximately 10 mm horizontally, whilein one patient (Case 4) it was only 7.25 mm. In three of the patients, thediameter of the eye could be determined. In Case 1, measurements atsurgery revealed the diameter to be 16 mm at the equator. In Case 4, theequatorial diameter was found to be 13 mm. Case 4 was later studiedhistologically, the fixed specimen having an equatorial diameter of 13.4mm. Case 5 was studied by ultrasonography and the anteroposteriorlength ofthe two eyes was 16.5 and 17 mm. An unusually thick sclera (2.5mm), which is apparently part of this syndrome, was observed in the twopatients (Cases 1 and 4) which underwent sclerotomy for drainage ofsubretinal fluid. In the other three patients, the scleral thickness couldnot be measured.With two exceptions, laboratory and general medical evaluation failed

to provide any consistent findings which might be related to the ocularabnormalities.

First, analysis of subretinal fluid from two patients (Cases 1 and 4) failedto show hyaluronic acid. Since hyaluronic acid is a component of thevitreous, it is found in the subretinal fluid of patients with rhegmatogen-ous retinal detachment. 10"11. 2 However, in the case of a secondary retinaldetachment with no retinal break, hyaluronic acid cannot enter thesubretinal space. Therefore, in the two patients in which this analysis wasperformed, the retinal detachment was proven to be of a secondary type.

Second, analysis of the cerebrospinal fluid showed elevated total pro-tein levels but no pleocytosis in two of the four patients in which this testwas performed (Cases 1 and 2). The presence ofan elevated cerebrospinalfluid total protein in patients with choroidal elevation and secondaryretinal detachment has previously been described. The ocular conditionhas been named uveal effusion.10 In contrast to Harada's disease, pa-tients with uveal effusion do not exhibit alopecia, poliosis, vitiligo,dysacousia, or lymphocytosis in the cerebrospinal fluid. However, thecerebrospinal fluid total protein is often elevated. Moreover, eyesaffficted with uveal effusion fail to show any significant signs of anteriorsegment inflammation. In this series, none of the patients exhibited thehallmarks of Harada's disease and there was no significant sign of anteriorocular inflammation. Thus, it is apparent that these five cases representan unusual type of uveal effusion which occurs in highly hyperopic, smalleyes and becomes evident only after the patient has been operated uponfor glaucoma accompanied by extremely narrow anterior chamber angles.The importance of recognizing this condition is emphasized by Case 4,

in which choroidal elevation was mistakenly diagnosed as a possible

Nanophthalmos 397

malignant melanoma and enucleation of the eye was performed. In thispatient, the diagnosis of malignant melanoma was corroborated by thelocalized decrease in transillumination. However, histologic examinationsubsequently revealed that the reduced transmission of light through thechoroidal elevation was probably the result of hemorrhage which oc-curred after drainage of subretinal fluid. Although a radioactive phos-phorus (P32) uptake test was not performed in Case 4, it is unlikely thatsuch a procedure would have been helpful. P32 tests performed in threeexamples of uveal effusion have revealed markedly increased uptake(100-300%) over the areas ofchoroidal elevation 48 hours after injection ofradioactive phosphorus.14 Thus, a false positive P32 test may occur inuveal effusion without the presence 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 detach-ment after glaucoma surgery, a conventional retinal detachment opera-tion failed. It has already been reported that retinal detachment surgeryusually is followed by complete loss of vision in cases of uveal effusion. 10

Finally, since retinal detachment did not occur until after surgery forglaucoma, it would appear advisable to exhaust all medical measures forthe control of glaucoma before resorting to surgery in eyes withnanophthalmos. The most beneficial treatment of nanophthalmic eyesexhibiting secondary retinal detachment appears to be the use of systemicsteroids. In four of the five cases reported (Cases 1, 2, 3 and 5), suchtherapy resulted in partial reattachment of the retina with visual im-provement. The best results are obtained with relatively high dosages.Unfortunately, however, such treatment is only palliative and it is appar-ent that relapses often occur, requiring repetition of the therapeuticregimen. Moreover, it is obvious from the results of Case 1 that steroidtherapy may be beneficial at one time but fail during a later relapse. Theresponse of choroidal elevation to steroid therapy is usually not complete.In Cases 3 and 5, although the retinal detachment responded to steroidtherapy, the choroidal elevation persisted, although to a lesser degree.The mechanisms responsible for this syndrome are not apparent from

the data of these five cases. The clinical findings and the course of thedisorder do not seem to imply an inflammatory basis. Instead, somegenetic predisposition seems to result in a failure of the eye to grow toproper dimensions, the anterior chamber being very narrow. Uveal effu-sion characterized by diffuse choroidal detachment, especially in theperiphery, may then occur (Figure 24). As choroidal elevation becomesmore marked, the iris root is rotated so that the filtration angle isobstructed and glaucoma occurs (Figure 25). Following surgery for

398 Brockhurst

Nanophthalmos

2a4

aFIGURE 24

Cross-section drawing of nanophthalmic eye with thick sclera, thickenedchoroid, and diffuse choroidal detachment which is more marked

peripherally.

399

Brockhurst

7ZzIbFIGURE 25

With further progression of the peripheral choroidal detachment, the irisroot is rotated so that the filtration angle is obstructed and glaucoma

occurs.

400

Nanophthalmos

CFIGURE 26

Drawing showing extensive secondary retinal detachment after glaucomasurgery. Note an iridectomy has been performed on right side.

401

IP.,-,

glaucoma, extensive secondary retinal detachment occurs (Figure 26).Unfortunately, in none of these five patients was the extreme fundusperiphery carefully examined prior to the onset of glaucoma. The occur-rence of glaucoma in the fourth to sixth decade of life would seem toindicate that the developmentally narrow angle has finally been embar-rassed, probably by an unrecognized peripheral choroidal elevation, andglaucoma ensues, requiring surgical therapy. Following this traumaticinsult to the eye, an imbalance in the dynamics of the circulatory systemof the globe appears to occur with additional thickening ofthe choroid andaccumulation of subretinal fluid. Analysis of subretinal fluid from a case ofuveal effusion15 revealed that this fluid contains an unusually largeamount of albumin (27.5 Gm percent), one acid phosphatase isoenzymenormally found in plasma, and no inflammatory cells. This indicates anabnormal permeability of the choriocapillaris to the smaller proteinmolecules of plasma and the absence of an inflammatory basis for uvealeffusion. Why such a situation should exist in small hyperopic eyes is yetto be explained.

SUMMARY

Five cases are presented, exhibiting a group of clinical features whichhave not been previously reported as occurring in the same individual. Inview of the fact that two of the patients were siblings and one otherpatient had a sibling with apparently similar anatomical changes, a famil-ial predisposition without sex preference is suggested. The syndromeincludes a high degree of hypermetropia (over + 13 diopters), smallcorneal diameter (approximately 10 mm), narrow anterior chamber an-gles, glaucoma occurring in the fourth to sixth decade of life and requiringsurgical intervention for control, and the development of choroidal eleva-tion and secondary retinal detachment following such surgery.

Anatomical study revealed a small global diameter varying from 13 mmto 17 mm, and an extremely thick sclera. Histologic examination showednarrow anterior chamber angles with frequent peripheral anteriorsynechiae, a thickened choroid with mononuclear cells, and degenerationof the external nuclear layer of the retina as well as of the rods and cones.Degeneration of the pigment epithelium was present histologically andconfirmed by fluorescein angiography. Analysis of subretinal fluid in suchcases failed to show any hyaluronic acid, indicating a secondary detach-ment. The presence of serum albumin and a plasma phosphatase isoen-zyme suggests that the subretinal fluid originated from blood plasma.

402 Brockhurst

General medical evaluation of these patients was essentially noncon-tributory, but the cerebrospinal fluid total protein was elevated in onehalf of the patients in which this analysis was performed. This findingindicates the unusual association of a small, extremely hyperopic eye(nanophthalmos) with uveal effusion.

Recognition of this disorder is stressed for several reasons. First,choroidal elevation may be mistakenly diagnosed as malignant melanomaof the choroid and unnecessary enucleation of the globe may be per-formed. Second, customary retinal detachment surgery should beavoided, since cases of uveal effusion respond unfavorably to such treat-ment. Third, glaucoma occurring in nanophthalmic eyes should prefera-bly be managed by medical means rather than surgical procedures, inorder to prevent the development of secondary retinal detachment.

Proper treatment of secondary retinal detachment is also discussed. Atthe present time, systemic steroid therapy appears to be the most effec-tive method in reducing the extent of the retinal detachment.

REFERENCES

1. Black M: Twins with high hyperopia. Am J Ophthalmol 7:375-376, 1924.2. Southgate PT: High hypermetropia. Am J Ophthalmol 33:466467, 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. AmJ Ophthalmol 36:983, 1953.6. Rathschuler R, Dufour R: Pathologie de l'hypermetropie forte. Ophthalmologica

129:327-330, 1955.7. Vetter J: Ablatio retinae als zweiterkrankung bei mikrophthalmus und glaukom. Klin

Monatsbl Augenheilkd 134:421426, 1959.8. Zuccoli A: Neuer beitrag zum bild der makrozysten bei der hohen hypermetropie.

Ophthalmologica 145:419424, 1963.9. Duke-Elder S: System of ophthalmology. Vol III Normal and Abnormal Development.

Pt. 2 Congenital Deformities. St. Louis, C.V. Mosby Co, 1963, pp. 488495.10. Schepens CL, Brockhurst RJ: Uveal effusion, I. Clinical picture. Arch Ophthalmol

70:189-201, 1963.11. Godtfredsen E: Investigations into hyaluronic acid and hyaluronidase in the subretinal

fluid in retinal detachment, partly due to ruptures and partly secondary to malignantchoroidal melanoma. BrJ Ophthalmol 33:721-732, 1949.

12. Sweeney B: Discussion in Controversial Aspects of the Management of Retinal Detach-ment. Edited by C.L. Schepens and C. D.J. Regan. Boston, Little Brown, 1965. pp.315-316.

13. O'Grady RB: Nanophthalmos. Am J Ophthalmol 71:1251-1253, 1971.14. Brockhurst RJ: unpublished data.15. Brockhurst RJ, Lam KW: Uveal Effusion. II Case report with analysis of subretinal

fluid. Arch Ophthalmol 90:399401, 1973.

Nanophthalmos 403