Autosomal recessive nanophthalmos

ACTAOPHTHALMOLOGICA SCANDINAVICA 1997 -

Autosomal recessive nanophthalmos Aygegul Koqak Altintag, Mehmet Akif Acar, Ilgaz Sagdiq Yalvaq, h c i Koqak, Ayge Nurozler and Sunay Duman S. B. Ankara Hospital, Ankara, Turkey

ABSTRACT. Nanophthalmos is a rare congenital ocular malformation which is generally recognized at middle age when serious complications have already developed. In this report 7 early diagnosed nanophthalmic cases are presented and diagnostic criteria, complications, inheritance and various modalities of treatment are discussed. Key words: nanophthalmos - microphthalmia - genetic penetrance - glaucoma.

Acta Ophthalrnol. Scand. 1997: 75: 325-328

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anophtalmos is a relatively rare developmental anomaly representing the arrested growth of the globe in the period between 7th week to 8th month of gestation, after the closure of the embryonic fissure. In this condition the eye is reduced in size without the presence of other ocular congenital anomalies or systemic developmental abnormalities (Calhoun 1975; Jin & Anderson 1990). In nanophthalmos, as the eyes are deeply set in the orbital cavities, the palpebral fissures are narrow. The normal axial length of the globe is 17 mm at birth and it increases to 23 mm at 3 years of age. After 3 years the globe grows 0.1 mm each year up to 14 years, until 24 mm which is the adult level. Because of the short axial length of the globe (< 20 mm) high hyperopia (+ 10.00 - + 20.00 D.) is the most characteristic feature of this condition. But, unusually, myopia may develop depending on the corneal refractive power (Calhoun 1975; Jin & Anderson 1990; Stewart et al. 1991; MacKay et al. 1987; Duke-Elder 1964; Susanna 1993). The normal anterior chamber depth is 2.3-2.7 mm at birth and 3 mm in hyperopic adults. The normal corneal diameter is between 9.5- 10.5 mm at birth and grows up to 12 mm in adults (Calhoun 1975; Wilmer & Scammon 1950). Small cornea, shallow anterior chamber and thickened sclera are the other features of nanophthalmos. There is no typical fundus finding.

In this report, we present 7 cases of nanophthalmos and discuss diagnostic criteria complications, genetic mode and penetrance, and treatment modalities.

Cases We studied 7 cases of familiar nanophthalmos in three families. We tried to examine all the family members in order to assess the genetic mode and penetrance. Fourteen individuals in the first family were examined. One brother (case I) and sister (case 11) aged 5 and 7 years and

their double first cousin aged 10 years (case 111) were affected. As shown in the pedigree (Fig. 1) the parents in the two affected family were cousins. Cases IV and V, aged 13 and 22 years were descendants of a non-consanguineous marriage. They were highly hyperopic, while the third child and the parents were normal. The family reported no other relative wearing high power glasses. Cases VI and VII were children of a consanguineous couple (third family). They were 23 and 25 years old and wore high power hyperopic glasses. Although not examined, neither the parents nor any of the relatives complained about any problems with their eyes. Three of the patients were male and four were female. The ophthalmic examination included refraction, slit-lamp examination, intraocular pressure (IOP), gonioscopy, fundus examination, colour vision and binocular single vision tests. Both A and B mode ultrasonography (USG) were performed and three patients had electroretinography (ERG). One of the patients (case Vl) refused further examinations

Fig. 1. Pedigree of family I.

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Table 1. Refractive power, corneal diameter and biometric values of the cases.

Case I Case I1 Case I11 Case IV Case V Case VI Case VII

R/L

VA

R L R L R L R L R L R L R L

0.1

0.1 0.2 0.2 0.8 0.2 0.3 0.3 0.6 1.0 0.2 0.3 0.1 0.1

Lens power

+ 15.00 + 15.00 + 13.00 + 13.00 + 9.00 + 9.00 + 15.00 + 15.00 +13.00 +1 3.00 +14.00 +15.00 +13.00 + 14.00

Corneal diameter

AC depth

Axial length

9.O mm 9.0 mm 9.2 mm 9.2 mm 9.8 mm 9.8 mm 10.1 mm 10.2 mm 10.9 mm 10.8 mm 9.7 mm 9.8 mm 9.6 mm 9.7 mm

2.0 mm 2.1 mm 1.77mm 1.92 mm 2.07 mm 2.07 mm 2.5 mm 2.4 mm 1.85 mm 1.81 mm 2.2 mm 2.3 mm 2.5 mm 2.5 mm

14.3 mm 14.0 mm 14.53 mm 14.64 mm 16.49mm 16.31 mm 16.83 mm 16.65 mm 16.23 mm 16.15 mm 16.15 mm 15.93 mm 14.75 mm 14.75 mm

~~

other than visual acuity, refraction and USG. The best corrected visual acuities of the patients were between 1/10 and 10/ 10. The hyperopic corrections were between + 9.00 D and + 15.00 D. Corneal diameters were measured with slitlamp (Table 1). Anterior chamber depths and axial lengths were measured with A mode Ultrasound (Fig. 2). B mode ultrasonography revealed diffuse choroidal thickening in all of the cases (Fig. 3). All of the patients were examined by the same physician (k)and no systemic abnormality was found. 1 0 P was measured in every examination for each patient. In three of our seven cases (Cases I, 11, 111) the IOP increased within a follow-up period of 3-7 months (mean 5.3 months). The IOPs were over 26 mmHg in cases I and I1 and fell below 2 1 mmHg with the treatment of beta blockers. In case 111, as the IOP in-

Fig. 2. Axial length of case 111 of the first family.

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creased to 28 mmHg after 3 months under medical treatment, we performed bilateral YAG laser iridotomies and the IOPs decreased to normal levels. Gonioscopic examination showed narrow angle with only a slit opening, no peripheral anterior synechia or congenital remnant was seen in any of the cases (Fig. 4). Colour visions were tested with Ishihara’s colour plates and were normal in all cases. Fusions were normal with Bagolini’s glasses and Worth’s four dot tests, both for near and distance vision. No patient had stereopsis as measured with TNO test. In our ERG laboratory normal b-wave amplitude is 150 f 30 microvolts and the implicit time is 3 milliseconds (ms) in photopic state and 350 f 50 microvolts with 80 ms implicit time in scotopic state. In case I; b-wave amplitude was 136 microvolts with implicit time of 31 ms in

photopic and 246 microvolts with 84 ms in scotopic state. Case III’s b-wave amplitude was 117 microvolts with 33 ms in the light adapted and 263 microvolts with 78 ms in the dark adapted state. ERG was within normal range in case IV, b-wave amplitudes were 126 microvolts in photopic and 348 microvolts in scotopic stage with normal implicit times. Fundus examination of cases I and I1 showed small optic discs, attenuated retinal vessels, horizontal retinal fold in the papillomacular region involving the fovea, and drusen-like deposits with pale mottled appearance in midperipheral retina in both eyes (Fig. 5). In case I11 the discs were mildly crowded, the retinal vessels and the maculae were normal. Foveolar reflexes were intact. In midperipheral fundus there was a peculiar pale mottled appearance and multiple tiny yellow white drusen-like deposits. Fundus examination of case Tv and V revealed vertically oval small optic discs. There was so-called salt and pepper appearance. In case VII, the optic discs were small with Bergmeister’s anomaly. The maculae were highly pigmented and there was no foveolar reflex. There were tiny retinal folds extending from the fovea to the lower nasal quadrant.

Discussion All of the eyes in our series were extremely hyperopic with a congenital axial hyperopia of + 10.00 D or more sphere. This was confirmed by USG. B mode USG showed the typical small globe and A mode documented the extremely short axial lengths. The upper limit of the axial

Fig. 3. B-mode USG of case V of the second family. Diffuse choroidal thickening can be seen.

ACTAOPHTHALMOLOGICA SCANDINAVICA 1997 -

Fig. 4. Gonioscopy of case I in first family. A narrow angle with only a slit opening.

length in nanophthalmos has been reported between 18 and 20.5 mm by different authors (Jin & Anderson 1990; Stewart et al. 1991; Duke-Elder 1964; Weiss et al. 1989; Singh et al. 1982). In all of our cases the axial lengths were less than 18 mm and the anterior chamber depths were below the normal range. The size of the lenszs in nanophthalmos are within normal ranges, therefore the lendglobe volume ratio which is 4% for normals increases up to the pathologic level of 10-30%. This relatively large lens size causes a forward displacement of the iris lens diaphragm and makes examination of the angle very difficult in gonioscopy. This condition limited the examination in our patients and the angles were narrow without peripheral anterior synechia formation in any of the cases. As the lens volume increases with time, patients with nanophthalmos are prone to develop angle closure glaucoma, especially between the 4th and 6th decades (Calhoun 1975; Jin & Anderson 1990; Stewart et al. 1991). Response to medical treatment is poor and miotics may even make the condition worse by producing relative pupillary block by relaxing the lens zonules. Conventional glaucoma surgery must be avoided in nanophthalmos because of the high risk of postoperative complications such as ciliary block, malignant glaucoma, massive uveal effusion, exudative retinal detachment and intraocular haemorrhage (Jin & Anderson 1990; Brockhurst 1975; Singh et al. 1982; Allen et al. 1988). Uveal effusion may also occur after laser treatment or indeed spontaneously (Kimbrough et al. 1979; Ryan et al. 1982; Good & Stern

Fig. 5. Fundus photography - . . of case I1 of the first family. Retinal fold in the papillomacular area involving the fovea can be seen.

1988; Gass & Jallow 1982; Morita et al. 1993; Brockhurst 1990). Our cases were very young compared with other nanophthalmic cases reported in the literature. At the initial examination none of our patients had any IOP problem. The patients were examined every 2 months and the IOPs were checked during the examination. Three of our patients developed high IOP levels during their follow-up at the ages of 5 , 7 and 10 years. To our knowledge, in the current English literature our patient at age 5 year is the youngest reported nanophthalmic patient with a high IOP problem. Two of the patients responded well to topical beta blocker treatment, but the third, who was 10 years old, needed Nd.YAG laser iridotomy, which could be done without any complication, and IOP decreased to normal levels. Fundoscopy of our cases revealed various features such as Bergmeister's papilla, small and moderate crowded optic nerve head, marked blood vessel attenuation, macular hypoplasia, retinal folds in the papillomacular region involving the fovea, and tiny drusen-like deposits in the midperipheral retina. Although there is no described typical fundus changes for nanophthalmos, some of our findings were similar to those reported by Calhoun (1975), Spitznas (1983) and MacKay et al. (1987). There were no foveal reflex in most of our cases. In case I and 111, who had drusen-like deposits with a pale mottled appearance in the midperipheral fundus, the E R G S were subnormal with a diminished b-wave amplitude and delayed b-wave implicit time in both photopic and sco-

topic stages. In case IV of the second family who presented with a salt and pepper appearance in the fundus, the ERG was within the normal range. Stewart et al. (1991) reported a series of 10 cases; in four of them, brothers and sisters had small eyes and hyperopia and they pointed out the possibility of a genetic defect in familiar nanophthalmos. In the family reported by Cross & Yoden (1976), heredity was likely to be recessive or X-linked, with expression possible in some female carriers. But MacKay et al. (1987) reported a familiar nanophthalmos with autosomal recessive, not X-linked penetrance. The parents of the patients in the 1.and 3. family were first degree relatives. The brothers and sisters of case 111 in the 1. family and the sister of case IV and V in the 2. family were normal. The history of consanguineous marriage in 2 of the families is shown in pedigrees (Fig. I). The disease affected both sexes and all of the parents in the three families were normal. It seems more likely that the penetrance in nanophthalmos is autosomal recessive and it may be seen more frequently in countries where consanguineous marriages are common. The simultaneous occurrence of nanophthalmos, angle closure glaucoma and retinal degeneration is extremely rare and the diagnosis of nanophthalmos in these cases may not be appropriate. Brochurst reported pigmentary degeneration in macula in 2 of his 3 cases of nanophthalmos. One of these cases was a child of a consanguineous couple, 2 of the brothers were hyperopic and one had glaucoma. These findings supported the re*_" 3LI

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cessive nature of this disease. MacKay et al. (1987) described a distinct autosomal recessive syndrome with nanophthalmos angle closure glaucoma and cystic macular degeneration. Our cases had similar findings with MacKay’s syndrome, but as none of our cases had anterior chamber abnormalities or cytic macular degeneration which is one of the main characteristic features of this syndrome, it was not possible to describe our cases as MacKay’s syndrome. As none of our cases had any facial or other systemic abnormalities, differential diagnosis with other syndromes with nanophthalmos was easy. As three of the cases had high IOPs during follow-up although they were normal at the initial examination, it would be a good idea to measure IOP regularly in patient with nanophthalmos, regardless of age, in order to diagnose the complication of glaucoma as early as possible. When examining a patient with high hyperopia it is important to keep the possibilityof nanophthalmos in mind and if possible the family members must be examined, especially if there is a history of consanguineous marriage. With a larger number of patients it may be possible to describe the characteristics of new syndromes with nanophthalmos.

References Allen KM, Meyers SM & Zegorra H (1988): Nanophthalmic uveal effusion. Retina 8: 145.

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Brockhurst RJ (1990): Cataract surgery in Nanophthalmic eyes. Arch Opthalmol108: 965-967. Brockhurst RJ (1975): Nanophthalmos with uveal effusion. A new clinical entity. Arch Ophthalmol93: 1289. Calhoun FP Jr (1975): The management of glaucoma in nanophthalmos. Trans Am Ophthalmol SOC73: 97. Cross HE & Yoden F (1976): Familial nanophthalmos. Am J Ophthalmol, 81: 300306. Duke-Elder S (1964). System of Ophthalmology, pp 488-495. CVMosby Co., St. Louis. Gass JDM & Jallow S (1982): Idiopathic serous detachment of the choroid, ciliary body and retina (uveal effusion syndrome). Ophthalmology 89: 1018. Good WV & Stern WH (1988): Recurrent Nanophthalmic uveal effusion syndrome following laser trabeculoplasty. Am J Ophthalmol106(2): 234-235. Jin CJ &Anderson DR (1990): Laser and unsutured sclerotomy in Nanophthalmos. Am J Ophthalmoll09: 575-580. Kimbrough RL, Trempe CS, Brockhurst RJ & Simmons RJ (1979): Angle closure glaucoma in nanophthalmos. Am J Ophthalmol 88(22): 572. MacKay CJ, Shek MS, Carr RE, Yanuzzi LA & Gouras P (1987): Retinal degeneration with nanophthalmos, cystic macular degeneration, and angle closure glaucoma. Arch Ophthalmol105: 366-371. Morita H, Funata M, Kusakari T, Yashino Y & KiyasawaM (1993):Recurrenceofnanophthalmic uveal effusion. Ophthalmologica 207: 30-36. Ryan CA, Zwaan J & Chylock LT (1982): Nanophthalmos with weal effusion. Clinical and embryologic considerations. Ophthalmology 89: 1013.

Singh OS, Simmons W, Brockhurst RJ & Trempe CL (1982): Nanophthalmos: a perspectiveon identification and therapy. Ophthalmology 89: 1006-1012. Spitznas M, Gerke E & Bateman JB (1983): Hereditary posterior microphthalmos with papillomacular fold and high hyperopia. Stewart DH, Streeten BW & Brockhurst RJ (1991): Abnormal scleral collagen in nanophthalmos. Arch OphthalmollO9: 10171025. Susanna R (1993): Implantation of an Intraocular lens in a case of Nanophthalmos. CLAO Journal 13(2): 117-118. Weiss AH, Kouseff BG, Ross LA & Longbotton J (1989): Simple microphthalmos.Arch OphthalmollO7 1625-1630. Wilmer HA & Scammon RE (1950): Corneal dimensions in newborn and adults. Arch Ophthalmol43: 599-620. Received on March 26th, 1996.

Corresponding author: Aysegiil K. Altintas S.B. Ankara Hastanesi Kenedi cad. No: 72/12 Kavaklidere 06660 Ankara, Turkey.