Aetiology Ofsevere Visual Impairment and Blindness in Microphthalmos 333

332 BritishJournal ofOphthalmology 1994; 78: 332-334

Aetiology of severe visual impairment and blindness in microphthalmos Br J Ophthalmol: first published as 10.1136/bjo.78.5.332 on 1 May 1994. Downloaded from

Mark J Elder

Abstract a group of patients with microphthalmos who Microphthalmos occupies a spectrum from were bilaterally legally blind. a normal, but small globe, to a globe with multiple anterior and posterior segment abnormalities. This study examines 54 eyes of 27 Patients and methods patients who had bilateral microphthalmos and All six academic blind schools of the West Bank severe visual impairment or blindness. Con- and Gaza strip were visited prospectively, and genital cataract was the commonest cause of the children examined. 6 There were 241 children severe visual impairment (44%), followed by aged from 5 to 25 years with visual acuities less presumed retinal or optic nerve displasia (30%) than 6/60, irrespective of their ocular diagnosis. and chorioretinal coloboma (22%). Lensec- There were no exclusion criteria. tomy was followed by phthisis bulbi in 3/23 Each school was visited by the 'Outreach' cases and retinal detachment in 2/23 cases. facility of the St John Ophthalmic Hospital, There were no cases of angle closure glau- Jerusalem, which is a well equipped mobile coma. The three clinical conditions associated clinic. A complete history was taken and the with a poor prognosis were cataract, chorio- previous medical records were reviewed. A full retinal coloboma, and a markedly reduced examination was conducted, including best cor- corneal diameter. A corneal diameter of 6 mm rected visual acuity with Sheridan-Gardner test or less was associated with a visual acuity ofno charts, colour vision assessment, visual field perception of light in 81% (21/26) compared testing by confrontation, slit-lamp biomicro- with 4% (1/28) ofthose with larger corneas. scopy, retinoscopy, cycloplegic refraction, and (BrJ Ophthalmol 1994; 78: 332-334) funduscopy. The corneal diameters were measured as the horizontal meridian from 'white to white' using the adjustable length of the light Microphthalmos is an ocular defect where the beam of a standard Topcon slit-lamp. When overall size of the globe is smaller than normal. indicated, children were sent to the base hospital The condition has been classified into simple or for further investigations such as ultrasound. All complex microphthalmos. '- Simple micro- microphthalmic patients in this study were

phthalmos is where the globe is small, but examined by the author. http://bjo.bmj.com/ otherwise normal. This is also called pure micro- The criterion for inclusion was bilateral microphthalmos or nanophthalmos. Complex, or com- phthalmos with a best corrected visual acuity of plicated, microphthalmos is where the globe has less than 6/60 in the better seeing eye. This other associated abnormalities. Both types may corresponds to the standard WHO definitions of be associated with an orbital cyst or other sys- reduced childhood visual acuity of severe visual temic abnormalities or syndromes. In general, impairment (>6/60 to 3/60) and blindness

microphthalmos is congenital but occasionally (>3/60 to no perception of light (NPL)). Statis- on October 3, 2021 by guest. Protected copyright. may be acquired because of arrested develop- tical analysis used X2 with a Yates' correction. ment. Microphthalmos can be defined as an eye with an axial length more than 2 SD smaller than the Results normal for that age group. This equates to an Within the total of 241 patients examined, there axial length less than 19-2 mm at age 1 year and were 27 patients with bilateral microphthalmos less than 20-9 mm as an adult.' There is a strong who had a visual acuity ofless than 6/60 and were linear correlation between the horizontal corneal examined by the author. The mean age was 10 3 diameter and the axial length from diameters of years and ranged from 5 to 20 years. A positive 2 mm to mm.' family history was present in 37%. The aetiology The ocular abnormalities associated with com- of visual impairment was divided into three plex microphthalmos are broadly subdivided categories; cataract, retinal, and unknown. Each into anterior segment dysgenesis, lens abnor- eye was allocated to its respective category by malities, chorioretinal coloboma, retinal dys- clinically determining the factor which was the plasia, and persistent hyperplastic primary major contributor to the visual impairment. vitreous (PHPV).'-"2 Syndromes associated with These data, along with other ocular abnor- microphthalmos number more than 100 and all malities, are detailed in Tables 1-3. Nystagmus St John Ophthalmic modes of inheritance have '3 Hospital, PO Box 19960, been described. was present in all cases. There were no cases of Jerusalem, Israel Systemic syndromes include the Hallerman- simple microphthalmos and no patient had facial M J Elder Strieff syndrome,'4 the Meckel-Gruber syn- malformations. Clinically, the vitreous, retina, Correspondence to: drome, trisomy 13, and the cerebro-oculofacio- and optic nerve head were able to be visualised Mark Elder, 36 Sinclair Road, 13 1" London W14 ONH. skeletal (COFS) syndrome. and examined unless stated otherwise. Accepted for publication The aim of this study was to determine the Within the cataract group, all patients had a 24 November 1993 main mechanisms causing impaired vision within diagnosis of cataract before the age of 6 months Aetiology ofsevere visual impairment and blindness in microphthalmos 333

Table I Bilateral blindness in microphthalmos primarily due to cataract and therefore had 'congenital' cataract. Only two patients had not had a previous lensectomy and Corneal Patient Age diameter Visual Primary cause Other ocular no patient had received an intraocular lens either No (years) (nm) acuity ofblindness abnormalities as a primary or a secondary procedure. Patient 2 Br J Ophthalmol: first published as 10.1136/bjo.78.5.332 on 1 May 1994. Downloaded from 1 5 8-5 3/60 Congenital cataract had no perception oflight bilaterally and 5 0 mm 8-5 3/60 Congenital cataract diameter corneas and surgery had not been 2 7 5 0 NPL Congenital cataract No fundal view 5 0 NPL Congenital cataract No fundal view offered. Patient 10 had a lensectomy in one eye 3 7 9 0 PL Congenital cataract Retinal detachment which revealed PHPV. This eye eventually had 9 0 NPL Congenital cataract Retinal detachment 4 7 8-0 HM Congenital cataract Thickened capsule NPL postoperatively and surgery was not per- 8-0 4/60 Congenital cataract formed in the other eye. Of the 23 lensectomies 5 8 8-0 PL Congenital cataract Macula coloboma 8-0 CF Congenital cataract Macula coloboma performed, the major complications were 6 9 7 0 PL Congenital cataract Aniridia, corneal scar phthisis bulbi (3/23) and retinal detachment 7 0 PL Congenital cataract Aniridia 7 10 4-0 NPL Congenital cataract Phthisis post surgery (2/23). Glaucoma was diagnosed after ocutome 4-0 NPL Congenital cataract Phthisis post surgery lensectomy in three eyes but it could not be 8 10 6-0 CF Congenital cataract Optic atrophy 6-0 NPL Congenital cataract Phthisis post surgery determined whether this was a primary abnor- 9 12 7 0 3/60 Congenital cataract mality or secondary to the surgery. The angles 8-5 1/60 Congenital cataract 10 13 5 0 NPL Congenital cataract PHPV were open in all cases. 5 0 PL Congenital cataract No fundal view Within the group of patients with a pre- 11 15 8-0 4/60 Congenital cataract 8-0 2/60 Congenital cataract Infantile glaucoma dominantly retinal cause for their blindness, 12 20 8-0 2/60 Congenital cataract Infantile glaucoma chorioretinal coloboma involving the macula 8-0 HM Congenital cataract Infantile glaucoma affected 12/14 eyes and myopic chorioretinal CF=counting fingers; HM=hand movements; NPL=no perception of light; PHPV=persistent degeneration affected 2/14 eyes. Other ocular hyperplastic primary vitreous; congenital cataract=cataract present before 6 months of age. abnormalities within this group were common. All patients except No 2 and the right eye of No 11 had previous lensectomies. Cataract was present in 4/14 eyes but in each case was mild and in another two cases had been Table 2 Bilateral blindness in microphthalmos primarily due to retinal abnormalities surgically removed. Mild cataract was defined as Corneal clinically insufficient to significantly impair the Patient Age diameter Visual Primary cause Other ocular visual acuity. No (years) (mm) acuity ofblindness abnormalities Table 3 details the group for whom a specific 13 5 9 0 4/60 Chorioretinal coloboma ON coloboma, cataract cause of visual impairment could not be deter- 8-0 3/60 Chorioretinal coloboma ON coloboma, cataract 14 8 8-0 CF Chorioretinal coloboma Squint mined. All but 2/16 eyes had NPL. In all cases, it 8-0 4/60 Chorioretinal coloboma Mild cataract was claimed that the child had been 'blind' from 15 10 5-5 PL Chorioretinal coloboma Iris dysplasia 6-0 NPL Chorioretinal coloboma Iris dysplasia, mild birth, rather than having a gradual deterioration cataract in vision. No eye had undergone surgery. The 16 13 9 0 1/60 Chorioretinal coloboma Cataract removed 9 0 2/60 Chorioretinal coloboma Cataract removed mean corneal diameters were smaller than in the 17 15 9 0 4/60 Chorioretinal coloboma cataract and retinal group; 5 0 mm v TI7 mm and 8-5 3/60 Chorioretinal coloboma 18 8 8-0 2/60 Chorioretinal coloboma 8-0 mm respectively. Six eyes had sclerocornea 8-0 PL Chorioretinal coloboma Retinal detachment and an adequate fundal view was not possible in http://bjo.bmj.com/ 19 10 8-0 5/60 Degenerative myopia -9 0 sphere 8-0 5/60 Degenerative myopia -9 0 sphere any of these 16 eyes. This was because of the small pupils which typically failed to dilate and, CF=counting fingers; HM=hand movements; NPL=no perception of light; ON=optic nerve. regardless, could not have dilated beyond 2-5-3-0 mm because of the size of the anterior Table 3 Bilateral blindness in microphthalmos with unknown aetiology segment. B scan ultrasound was performed on 10/16 of these eyes and this revealed no abnor-

Corneal on October 3, 2021 by guest. Protected copyright. Patient Age diameter Visual Ocular Fundal mality in the anterior or posterior segments in No (years) (mm) acuity abnormalities view any eye except for the decreased size ofthe globe. 20 7 4 0 NPL - No Electrophysiological investigations were not per- 4-0 NPL - No formed. The summary of best corrected visual 21 8 5 0 NPL - No 5 0 NPL - No acuity, compared with horizontal corneal 22 8 6-0 NPL - No diameter, is presented in Table 4. Those patients 6-0 NPL - No 23 10 6-0 NPL Sclerocornea No with corneal diameters greater than 6 mm were 6-0 NPL Sclerocornea No more likely to achieve an acuity of better than 24 11 6-0 NPL - No 6-0 NPL - No perception of light compared with those with 25 11 3 0 NPL - No smaller corneas (p<0-001). 3-0 NPL - No 26 13 4 0 PL Sclerocornea No 4 0 PL Sclerocornea No 27 18 6-0 NPL Sclerocornea No 6-0 NPL Sclerocornea No Discussion Previous classifications of microphthalmos have PL=perception oflight; NPL=no perception of light. been based on anatomical abnormalities. '` How- ever, it is useful for the clinician also to be able to Table 4 Best corrected visual outcome compared with estimate the ultimate visual outcome, especially corneal diameter when microphthalmos is often apparent early in Weiss et al' have shown that Corneal diameter life."'- previously simple microphthalmos is associated with a good Visual acuity v-6 mm >6 mm visual outcome with 21/22 patients achieving >6/60 to 1/60 - 18 better than 6/18 even though 82% had at least Counting fingers 1 2 +7-0 dioptres of hypertropia. In contrast, this Hand movements - 2 Perception of light 4 5 study looks at patients that ultimately became No perception of light 21 1 Total severely visually impaired or blind because of 26 28 microphthalmos. In keeping with Weiss et al's 334 Elder

series,' there were no patients with simple micro- visual acuity shows the marked tendency for eyes phthalmos within this study group. that have corneas less than or equal to 6 mm to The commonest cause of blindness was con- have a poor acuity. However, the corneal

genital cataract""'2 (44%, 24/54) and mild cata- diameter was measured in patients from age 5 to Br J Ophthalmol: first published as 10.1136/bjo.78.5.332 on 1 May 1994. Downloaded from ract was also present in another six eyes. 20 years and it is difficult to extrapolate this to Lensectomy had been performed on 23 eyes and findings in early infancy. In microphthalmos, the this had been followed by phthisis bulbi in three natural history of the growth of the cornea from eyes and retinal detachment in two eyes. There- birth to adulthood is unknown but it is pos§ible fore, 22% (5/23) of patients had a major compli- that it follows a similar pattern to normal eyes. A cation leading to, at best, perception oflight. The normal cornea has a horizontal diameter of 10 0 combination of microphthalmos and aphakia mm at birth and has reached adult dimensions of produces very high hypermetropia but for 11-8 mm by 2 years ofage.2223 By analogy, a 6 mm economic reasons (the per capital gross national cornea in adulthood is equivalent to a 5-1 mm product of the region is £100041300'7), no diameter cornea at birth (6 0x10O0/11 8=5 - child had a trial ofcontact lenses for the aphakia. mm).18 9 Therefore, a newborn child with micro- Chorioretinal coloboma involving the macula phthalmos and a corneal diameter of5 mm or less was the second commonest cause of blindness has a very poor visual prognosis. affecting 22% of eyes (12/54). It was also present The author acknowledges the help and assistance of Mr Romain to a mild degree in another two eyes. This group De Cock, FRCS and the Order of St John. of patients was also associated with cataract and iris dysplasia (7/12). Glaucoma overall was 1 Weiss AH, Kousseff BG, Ross EA, Longbottom J. Simple microphthalmos. Arch Ophthalmol 1989; 107: 1625-30. uncommon, affecting only three eyes, all of 2 Weiss AH, Kousseff BG, Ross EA, Longbottom J. Complex whom had previous cataract surgery. However, microphthalmos. Arch Ophthalmol 1989; 107: 1619-24. 3 Duke-Elder S. System of ophthalmology. Vol III. London: it was uncertain whether this was related to the Kimpton, 1964: 488-95. surgery. No patient had angle closure as has been 4 Bateman JB. Microphthalmos. Int Ophthalmol Clin 1984; 24: 87-107. previously noted in association with this condi- 5 Capella JA, Kaufman HE, Lill FJ, Cooper G. Hereditary tion.'8 cataracts and microphthalmia. AmJr Ophthalmol 1963; 56: 454-8. PHPV was found in only one eye in this series. 6 Francois J. A new syndrome: dyscephalia with a bird face and This is in accordance with the observation that dental abnormalities, nanism, hypotrichosis cutaneous atrophy, microphthalmia and congenital cataract. Arch PHPV is associated with microphthalmos almost Ophthalmol 1958; 60: 842-62. always in unilateral disease.' High myopia with 7 Haddad R, Font RL, Resser F. Persistent hyperplastic primary vitreous: a clinicopathological study of62 cases and degenerative chorioretinal degeneration affected review of the literature. Surv Ophthalmol 1978; 23: 123-43. both eyes of one patient and this may occur as a 8 Mann I. Developmental abnormalities of the eye. London: Cambridge University Press, 1937: 65-103. specific, inheritable entity.'9 9 Shields MB, Buckley E, Klintworth GK, Thresher R. The patients classified into the unknown Axenfeld-Rieger syndrome: a spectrum of developmental disorders. Surv Ophthalmol 1985; 29: 387-409. aetiology group remain a problem. In general, 10 Waardenburg PJ, Franceschetti A, Klein D. Genetics and these patients had the smallest eyes (mean cor- ophthalmology. Springfield, IL: Thomas, 1961: 880-1. neal diameter= 5-0 and a fundal view was 11 Witkop-Oostenrijk GA. Microphthaimia, microcornea and mm) congenital cataract. Ned Tijdschr Geneeskd 1956; 100: precluded because of sclerocornea (6/16), or a 2910-3. http://bjo.bmj.com/ 12 Zeiter HJ. Congenital microphthalmos. Am J Ophthalmol small pupil and the presence of nystagmus. 1%3; 55: 910-21. Sclerocornea is known to be associated with 13 Warburg M. An update on microphthalmos and coloboma. OphthalmolPaediatrGenet 1991; 12: 57-63. microphthalmos.20 However, the visual acuity 14 Falls HF, Schull WJ. Hallerman-Streiff syndrome. Arch was NPL in 14 and PL in the other two eyes. Ophthalmol 1%0; 63: 409-20. 15 Warburg M. Genetics of microphthalmos. Int Ophthalmol Ultrasound examination showed small globes but 1981; 4:45-65. normal vitreous and anterior segments. This, 16 Elder MJ, De Cock R. Childhood blindness in the West Bank and Gaza Strip; aetiology, prevalence and the influence of together with the history of being 'blind from hereditary factors. Eye 1993; 4: 580-3. on October 3, 2021 by guest. Protected copyright. birth', suggests that there was a severe primary 17 Health in Judea, Samaria and Gaza 1991. State of Israel, Ministry of Health, 1991. developmental defect in the retina or optic nerve. 18 Kimbrough RL, Trempe CS, Brocklehurst RJ, Simmons RJ. This is in keeping with Weiss et al's findings2 that Angle-closure in nanophthalmos. Am J Ophthalmol 1979; 88: 572-9. in complex microphthalmos, 80% had a mal- 19 Usher CH. A pedigree of microphthaimia with myopia and formation of the posterior segment. A clinico- corectopia. BrJ Ophthalmol 1921; 5: 289-99. 20 Goldstein JE, Cogan DG. Sclerocornea and associated con- pathological case report of a stillborn child with genital abnormalities. Arch Ophthalmol 1%2; 67: 99-106. Meckel-Gruber syndrome and microphthalmos 21 Jones KL. Smiths'srecognizable patternsofhuman malformation. Philadelphia: Saunders, 1988: 152-3. with corneal diameters of 4 0 and 6 0 mm 22 Hymes C. The postnatal growth of the cornea and palpebral showed severe retinal dysplasia and optic nerve fissure and the projection of the eyeball in early life. J Comnp Neurol 1929; 48: 415. dysplasia.2' 23 Duke-Elder S. System of ophthalmology. Vol II. London: The comparison of corneal diameter with Kimpton, 1961: 93-4.