Purpose
To investigate the clinical features and prognosis of congenital retinal folds without systemic associations.
Design
Retrospective observational case series.
Methods
The characteristics, clinical course, ocular complications, and best-corrected visual acuity (BCVA) of eyes with congenital retinal folds were studied during the follow-up periods. The affected and fellow eyes were examined by slit-lamp biomicroscopy, binocular indirect ophthalmoscopy, and fundus fluorescein angiography. The parents and siblings of each patient also underwent ophthalmoscopic examinations. The BCVA was measured using a Landolt ring VA chart.
Results
One hundred forty-seven eyes of 121 patients with congenital retinal folds were examined. Fifty-five patients (45.5%) were female. The fold was unilateral in 95 patients (78.5%), and 69 of those patients (72.6%) had retinal abnormalities in the fellow eye. The meridional distribution of folds was temporal in 136 eyes (92.5%). The family history was positive in 32 patients (26.4%). Secondary fundus complications, including fibrovascular proliferation and tractional, rhegmatogenous, and exudative retinal detachments, developed in 44 eyes (29.9%). The BCVAs could be measured in 119 eyes and ranged from 20/100 to 20/20 in 5 eyes (4.2%), 2/100 to 20/200 in 45 eyes (37.8%), and 2/200 or worse in 69 eyes (58.0%). The follow-up periods ranged from 4 to 243 months (mean, 79.7 ± 58.9 months).
Conclusions
These clinical features suggested that most congenital retinal folds may result from insufficient retinal vascular development, as in familial exudative vitreoretinopathy, rather than persistent fetal vasculature. Adequate management of active retinopathy and late-onset complications, especially retinal detachment, is required.
A congenital retinal fold (ablatio falciformis congenital), extending radially from the optic disc toward the peripheral fundus, was first described in 1935 as a rare congenital anomaly. The pathogenesis was investigated histologically, and the anomaly was hypothesized to be attributable to persistent hyaloid vessels leading to a pulled dysplastic retina. In 1955, Reese reported the clinical and pathologic features of persistent hyperplastic primary vitreous (PHPV). In 1965, Michaelson introduced the term “posterior PHPV,” and in 1970 Pruett and Schepens described a new clinical entity called “posterior hyperplastic primary vitreous,” the posterior form of PHPV, characterized by vitreous membranes extending from the disc toward the peripheral fundus. Those investigators used the term posterior PHPV as a synonym for falciform retinal folds and the term anterior PHPV as a synonym for the PHPV described by Reese. Thus, congenital retinal folds often were diagnosed as posterior PHPV afterward. The term PHPV now has evolved to persistent fetal vasculature (PFV), which usually occurs as a nonheritable set of vascular malformations affecting 1 eye of an otherwise normal infant. However, based on the fundus drawings of Pruett and Schepens, vitreous membranes and retinal folds were not clearly distinguished. Those authors reported that the vitreous band and retinal folds extended toward the fundus periphery in various meridians but were most commonly nasal. They also described the pleomorphism of posterior PHPV and complications such as microcornea, retinal detachment, vitreous hemorrhage, cataract, and glaucoma. In most cases, posterior PHPV is unilateral and rarely familial.
In 1969, familial (dominant) exudative vitreoretinopathy (FEVR), a developmental disorder of the retinal vasculature, was described and suggested to be the possible origin of congenital retinal folds. Recently, congenital retinal folds were thought to occur even after birth and were caused by various infantile diseases such as FEVR, retinopathy of prematurity (ROP), Norrie disease, incontinentia pigmenti, and congenital toxoplasmosis. However, clinically distinguishing retinal folds without systemic associations is often difficult, and their pathogenesis remains controversial.
We conducted the current study to clarify the clinical features of congenital retinal folds without systemic associations.
Methods
One hundred forty-seven eyes of 121 patients with unilateral or bilateral congenital retinal folds, diagnosed at the National Center for Child Health and Development, Tokyo, Japan, between June 1986 and February 2009, and examined between March 2002 and April 2009, were studied retrospectively. Patients with a history of premature birth, oxygen therapy, systemic associations, or positive laboratory examinations for infectious diseases were excluded. Eyes with anterior segment dysgenesis also were excluded.
The characteristics of retinal folds in affected eyes and findings in fellow eyes were examined by slit-lamp biomicroscopy and binocular indirect ophthalmoscopy. Thirty-six patients (29.8%) underwent fundus fluorescein angiography (FA) under general anesthesia. In patients with a unilateral retinal fold, the fundus periphery of the fellow eye also was examined and the retinal vascular development was evaluated. The criteria used to diagnose retinal vascular abnormalities were the presence of a peripheral avascular zone, vitreoretinal adhesions, arteriovenous shunt formation, supernumerous vascular branchings, a V-shaped area of retinal degeneration, neovascularization, and cystoid degeneration. Ophthalmoscopic examinations of the parents and siblings of each patient were performed when possible. A family history was judged to be present if retinal vascular abnormalities were found in any family members. The clinical course and the secondary ocular complications were investigated during the follow-up periods. The best-corrected visual acuities (BCVAs) were measured with a standard Japanese VA chart using Landolt rings at 5 meters and converted to Snellen VA. The follow-up periods ranged from 4 to 243 months (mean, 79.7 ± 58.9 months).
Results
Characteristics of Eyes and Patients
Sixty-six of the 121 patients (54.5%) were male and 55 (45.5%) were female. The ages of the patients at the first examination at our hospital ranged from 4 weeks to 9 years 1 month (mean, 17.9 ± 21.6 months). However, the families or pediatricians had observed the clinical manifestations, that is, poor fixation behavior, nystagmus, or strabismus, by 12 months of age in 105 patients (86.8%), and 91 patients (75.2%) had been examined by other ophthalmologists within the first year. A unilateral retinal fold in 16 patients (13.2%) identified after 13 months of age was confirmed not to have any acquired pathogenesis and diagnosed as a congenital retinal fold.
The retinal vessels within the fold were bundled and pulled toward the peripheral fibrous tissue and decreased in number in the stretched retina in 144 of 147 eyes (98.0%) ( Figure 1 , Bottom left). A peripheral avascular zone was seen more than 3 disc diameters’ width in all eyes. Other ophthalmoscopic findings in affected eyes were intravitreal neovascularization in 13 eyes (8.8%), retinal hemorrhages in 8 eyes (5.4%), disc anomalies in 4 eyes (2.7%), retinal exudates in 3 eyes (2.0%), and coloboma and medullated nerve fiber in 1 eye (0.7%) each. Fundus FA, performed on 46 eyes of 36 patients, showed hyperfluorescence from bundling of the retinal vessels in the folds and fibrovascular tissue at the periphery of the folds in all eyes (100%). Dye leakage from an arteriovenous shunt and intravitreal neovascularization within the fibrovascular tissue was detected in 13 eyes (28.3%) ( Figure 1 , Bottom right).
Most Cases of Congenital Retinal Fold Were Unilateral and Originated in the Temporal Quadrants
The fold was unilateral in 95 of 121 patients (78.5%) and bilateral in 26 patients (21.5%). The meridional distribution of the folds was temporal, superotemporal, or inferotemporal in 136 of 147 eyes (92.5%) ( Figure 2 ) . All folds in the other 11 eyes were unilateral, extending nasally, superonasally, inferonasally, superiorly, or inferiorly.
Most Cases of Unilateral Retinal Fold Had Identifiable Abnormalities in the Fellow Eye
Only 26 cases (27.4%) of the 95 unilateral retinal folds identified demonstrated no pathology in the fellow eye. The remaining 72.6% had identifiable abnormalities as follows. Retinal vascular abnormalities in the peripheral fundus were identified in 33 of 95 cases (34.7%): an avascular zone in all eyes (100%), supernumerous vascular branchings in 15 eyes (45.5%), cystoid degeneration in 12 eyes (36.4%), a V-shaped area of retinal degeneration in 9 eyes (27.3%), vitreoretinal adhesions and fibrous membrane in 7 eyes (21.2%) each, arteriovenous shunt formation in 5 eyes (15.2%), and neovascularization in 4 eyes (12.1%) ( Figure 1 , Top left and right). A total retinal detachment and leukokoria, a dragged retina, and coloboma were found in 18 (18.9%), 17 (17.9%), and 1 (1.1%) of 95 cases, respectively.
The “true” unilateral congenital fold was seen in 26 patients out of all 121 patients (21.5%). Among these 26 patients, the meridional distribution of the folds was temporal in 17 eyes (65.4%) and nasally, superiorly, or inferiorly in 9 eyes (34.6%).
Fundus FA was performed on 24 fellow eyes in patients with a unilateral retinal fold and clearly showed various retinal vascular abnormalities in 18 eyes (75.0%). Hyperfluorescence of the vascular abnormalities in the periphery was seen in 8 of the 24 eyes (33.3%), in which dye leakage from the neovascularization was detected in 4 eyes (4/24; 16.7%) ( Figure 1 , Top right).
Among the 50 fellow eyes with retinal vascular abnormalities in the periphery or dragged retina, laser photocoagulation was applied to the peripheral avascular retina in 7 eyes (14.0%) and the neovascularization stabilized in all eyes (100%). Scleral buckling was performed in 3 fellow eyes (6.0%) for a late-onset tractional or rhegmatogenous retinal detachment, and retinal reattachment was achieved in all eyes (100%).
Most Cases of Congenital Retinal Fold Suggest Familial Inheritance
Family members were examined in 50 cases (41.3%), and a positive family history was identified in 32 cases (64.0%), with ophthalmoscopic findings of retinal vascular abnormalities in the periphery (81.2%), retinal folds (9.4%), dragged retina (6.3%), and leukokoria (3.1%). A negative family history was suspected by ocular examination of the parents in 18 cases (36.0%). In all cases with a positive family history, the trait originated in 1 of the family lines. In positive cases, the fold was bilateral in 12 cases (37.5%) and unilateral with abnormal retinal vascular changes in the fellow eye in the other 20 cases (62.5%). In negative cases, the fold was bilateral in 5 cases (27.8%), unilateral with abnormal retinal vascular change in the fellow eye in 9 cases (50.0%), and unilateral with normal fellow eye in 4 cases (22.2%).
Secondary Complications of Congenital Retinal Fold are Common and Visually Devastating
During the follow-up periods, secondary ocular complications developed in the fundus in 44 of 147 eyes (29.9%) with congenital retinal folds; progression of a tractional retinal detachment in 19 eyes (12.9%), rhegmatogenous retinal detachment in 12 eyes (8.2%), fibrovascular proliferation from the neovascularization in 11 eyes (7.5%), and exudative retinal detachment in 2 eyes (1.4%). The secondary complications in the fundus of 44 eyes are summarized in the Table .
| Tractional Retinal Detachment N = 19 Eyes | Rhegmatogenous Retinal Detachment N = 12 Eyes | Fibrovascular Proliferation N = 11 Eyes | Exudative Retinal Detachment N = 2 Eyes | |
|---|---|---|---|---|
| Age at onset (months) | 1–88 (mean, 25.8 ± 27.2) | 33–195 (mean, 87.0 ± 56.5) | 2–121 (mean, 19.4 ± 35.8) | 31, 167 |
| Origin of complications |
|
|
| Unknown 2 (100%) |
| Treatment |
|
|
| None, 2 (100%) a |
| Surgical outcomes | Retinal reattachment, 7/10 (70%) | Retinal reattachment, 3/11 (27%) | NV stabilization, 8/10 (80%) |
Among the 26 patients with “true” unilateral congenital fold, secondary ocular complications also developed in the fundus in 6 eyes (23.1%); progression of a tractional retinal detachment in 2 eyes (7.7%), rhegmatogenous retinal detachment in 1 eye (3.8%), fibrovascular proliferation from the neovascularization in 2 eyes (7.7%), and exudative retinal detachment in 2 eyes (3.8%).
Tractional Retinal Detachments
Progression of tractional retinal detachment occurred in patients ranging in age from 1 to 88 months (mean, 25.8 ± 27.2 months). Among the 19 eyes the tractional retinal detachment originated from excessive fibrovascular proliferation and contraction in 15 eyes (79%) ( Figure 3 , Top and Middle) and regrowth of fibrovascular tissue in 4 eyes (21%). Ten eyes (53%) were treated: vitrectomy with lensectomy was performed in 6 eyes (32%) and scleral buckling with laser photocoagulation in 4 eyes (21%). Retinal reattachment was achieved in 7 of 10 treated eyes (70%).
