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Primary iris pigment epithelial hyperplasia (PIPH) is a rare condition characterised by the presence of iris pigment epithelium on the anterior surface of the iris stroma. There are few reports that are available in the literature1–11 and they generally refer to it as congenital ectropion uveae (CEU). CEU, however, is a misnomer, since the iris pigment layer is known to be separate from the uvea.7 Yet, the term CEU persists in clinical use.
Primary iris pigment epithelial hyperplasia is a congenital non-progressive condition that is easily differentiated from acquired progressive ectropion uveae, the latter resulting from tractional eversion of posterior pigment layer and sphincter muscle, secondary to glaucoma and/or uveitis.
This report describes two cases of primary iris pigment epithelial hyperplasia with glaucoma and reviews the available literature on this rare abnormality. In one case the presentation of glaucoma was in adolescence and in infancy in the other. Associated ocular features are described. In these two patients there were no systemic features of diagnostic significance.
A 15 year boy presented with occasional watering in the left eye for 4 years. There was no history of any visual disturbance.
On examination his left eye was apparently proptosed and Hertel exophthalmometry readings were 19 mm in the left eye and 13 mm in the right with bar reading of 105. He had a ptosis of 2 mm (Fig 1, top right) with good levator function. The appearance of the left upper lid was suggestive of plexiform neurofibroma but no mass was palpable. The patient's vision was 20/20 right eye (emmetropic) and 20/25 left eye (cylinder of −1.50 D at 110°, keratometry left eye −42.00 × 15°, 45.5 × 105°).
The left eye had extensive hyperplasia of the iris pigment epithelium which overlay the stroma of the iris in an irregular manner but did not reach the angle (Fig 1, top left). The normal iris architecture was lost, but no nodules were seen. There was pigment on the anterior surface of the lens but the iris did not transilluminate. There was anisocoria of 1.5 mm, the left pupil being larger but round, regular and reacting to light. Indirect gonioscopy (Fig 1, bottom left) demonstrated an open angle with iridotrabeculodysgenesis in the form of an anterior insertion of the iris into the trabecular meshwork with excessive pigment deposition and a prominent Schwalbe's line, this being very marked in some areas. The right eye had a fully open angle with all structures clearly seen. Intraocular pressure (IOP) on the first examination was 52 mm Hg in the left eye and 12 mm Hg in the right. On fundus examination there was an oblique insertion of the disc, with inferonasal crescent and an oval oblique cup involving 0.8:1 × 0.6:1 part of the disc (Fig 1, bottom right). A B-scan ultrasound of orbit did not reveal any abnormality and the A-scan biometry confirmed that the apparent proptosis of the left eye was due to a longer axial length (24.36 mm compared with 22.60 mm in the right eye). There were two cafe au lait spots on the trunk but there was no other systemic abnormality. None of the family members had similar ocular findings or any evidence of neurofibromatosis.
The IOP responded poorly to topical medication and a trabeculectomy was performed which controlled the IOP.
A 5½12 year old girl presented with gradual enlargement of the right eye since the age of 6 months. There was a history of mild photophobia but none of lacrimation or deterioration of vision.
On examination the patient's Snellen acuity was 20/240 in the right eye (−1.5D sph, −4.0D cyl × 90°) and 20/20 in the left eye (−0.25D cyl × 90°). The right eye was buphthalmic with a corneal diameter of 13.0 × 14.0 mm (10.5 × 11.5 mm, left eye). The right eye had extensive hyperplasia of the iris pigment epithelium overlying the stroma of the iris in an irregular manner, but this did not reach the angle. The normal architecture of the iris was lost but there were no iris nodules. The angle was examined with a direct gonioscope and the findings were similar to that of case 1. The right pupil was 6 mm in diameter and did not react to light and was less responsive to miotics and mydriatics.
Intraocular pressure was 27 mm Hg in the right eye (on oral acetazolamide and topical timolol and propine) and 14 mm Hg in the left eye. Fundus examination of the right eye revealed a 0.9:1 cupping of the optic disc with a significant pallor of the neuroretinal rim and bayonetting of the vessels. A-scan biometry demonstrated an axial length of 26.0 mm in the right eye and 22.07 mm in the left.
No systemic abnormality was detected. No sibling, parent, or near relative was similarly affected.
A combined trabeculotomy and trabeculectomy without any pharmacological modulation was performed on the right eye and a diffuse bleb and a well formed anterior chamber was seen on fourth postoperative day but intraocular pressure was unrecordably low. The patient's vision at 4 weeks postoperatively was 20/200.
In the normal iris the pigment epithelium forms a double layer that includes itself into the pupillary margins as the pigmented ruff. A congenital exaggeration of this process occurs where the pigmented layer advances over the anterior surface of the iris to a varying degree.10 The extent to which the pupillary circumference is involved in PIPH is variable,9, 11 but characteristically ends short of the angle.9 The pupil may be normal in size in some cases and larger than its counterpart in others.7 It may be round and reactive to light but may be oval9 and less reactive to light.7 The iris stroma is generally hypoplastic to a variable degree,9 with a smooth anterior surface with absence of circular concentric furrows and radial folds.7 The condition is usually unilateral5, 7, 9–11 but a bilateral case has been reported.8
Both the cases in this report had extensive PIPH, loss of normal iris architecture, and pupillary abnormalities.
The aetiology of the condition remains unknown but is probably due to imbalance of growth between the ectoderm and the mesoderm, usually a hyperplasia of the former.11 It may represent a clinical manifestation of a pathological process related to abnormal neural crest cell migration.7
Histological studies have shown that the eversion is the result of hyperplasia of the pigment epithelial layer.7 There is no evidence that the condition is hereditary in uncomplicated cases, however, those which are associated with conditions such as Rieger's dysgenesis may be transmitted in the same way as the major deformity.11
A variety of systemic disorders have been reported in association with PIPH. Neurofibromatosis is the disorder most commonly associated with PIPH.8, 9, 12 In one report9 three out of eight were associated with neurofibromatosis. In addition, Ritch et al9 reported neurofibromatosis, a case of associated diabetes mellitus and left facial hemiatrophy, and one each of Prader-Willi syndrome and right facial hemiatrophy. Hetzbert8 reported a case with associated asthma and a dental anomaly.
Not all cases have systemic associations. None of the nine patients reported by Dowling et al7 had any systemic associations. None of the two cases in this report had any identifiable systemic association.
Besides the iris and pupillary abnormalities discussed above, PIPH is frequently associated with significant ocular abnormalities. Ipsilateral mild ptosis with good levator function was presented in six of nine cases reported by Dowling et al7 and in one case each by Ritch et al9 and Herzberg.8 The eye may be slightly proptotic in some cases.9 The appearance of the upper lid may suggest plexiform neuroma even though no mass may be palpable.9 All these features were present in the first case in this report.
Angle anomalies appear to be universal in most of the cases demonstrating anterior insertion of the iris,7, 9 a prominent Schwalbe's line, prominent iris processes and/or increased pigment,9 and a similar iridotrabeculodysgenesis was present in both the cases in this present report.
Glaucoma was present in most of the cases reported. Ritch et al9 found glaucoma in seven out of eight cases of PIPH, Dowling et al7 in eight of nine cases, and it was also noted and in other reported cases of PIPH.2, 3, 5, 6, 8, 10, 12 It is usually of onset in childhood or early adolescence as was seen in cases in this report but cases with late onset also has been reported.1, 7, 10 The intraocular pressure shows an initial decrease when the medication is instituted but rises again quickly and filtering surgery was required in most cases.7
Surgical intervention was necessary in both the cases in this report.
The features of PIPH detailed in this report are in concordance with those previously published. There may be other associated ocular abnormalities, ptosis being the commonest. Neurofibromatosis is the most frequently associated systemic disorder.
Glaucoma may develop at any stage, therefore these cases should be recognised early by healthcare professionals and followed for development of glaucoma.