The clinical and morphologic spectrum of optic nerve hypoplasia.

PURPOSE: The purpose of this study was to characterize the clinical and morphologic spectrum of all children referred for optic nerve hypoplasia to a tertiary referral hospital in Sweden during a 9-year period. SUBJECTS AND METHODS: A retrospective review was undertaken of the charts of 117 children (age range, 0.25-16 years), treated at the Children's Hospital, G?teberg between 1988 and 1996, after the diagnosis of optic nerve hypoplasia. Ocular fundus morphologic condition was evaluated by digital image analysis of fundus photographs in 50 children, and neuroimaging was performed in 57 children. RESULTS: Of the 117 children with optic nerve hypoplasia, 66 (56%) were boys and 51 (44%) were girls. Preterm birth occurred in 24 (20%), and 14 (12%) were born small for gestational age. Additional diagnoses, such as fetal alcohol syndrome, septo-optic dysplasia, perinatal adverse events, and neuropsychiatric disorders, were made in 88%; 7% had unilateral optic nerve hypoplasia. Most of the children had small optic disc, cup, and neuroretinal rim areas, as well as retinal vascular abnormalities; 75% were visually impaired, and a high incidence of nystagmus and strabismus was found among these children. CONCLUSION: This study indicates that optic nerve hypoplasia has a wide clinical and morphologic spectrum and is associated with a broad range of disorders of the central nervous system. It is suggested that differences in the etiology and timing of the lesion as well as associated lesions may explain this spectrum of optic nerve hypoplasia in children.     

Clinical characteristics of high grade foveal hypoplasia

To report clinical characteristics of high grade foveal hypoplasia. Patients with foveal hypoplasia of grade 3 or 4 on spectral domain optical coherence tomography according to a previously published scheme were enrolled. All patients underwent a full ophthalmologic assessment including visual acuity testing, slit lamp biomicroscopy, fundus examination, and evaluation of ocular alignment. The underlying causes of foveal hypoplasia were identified as albinism in five patients and aniridia in six patients. The mean logMAR visual acuity was 0.57 ± 0.24 (range 0.22–1.00) in the right eyes and 0.58 ± 0.21 (range 0.30–1.00) in the left eyes. On fundus examination in patients with albinism, two patients showed marked transparency, one patient showed moderate transparency, and two patients showed minimal transparency. Among six patients with aniridia, five patients showed normal macular pigmentation without macular reflex and one patient showed decreased macular pigmentation with no macular reflex. Patients with high grade macular hypoplasia tended to have poor visual acuities; however, the range of visual acuity was quite variable. Other factors associated with underlying disease could be the reason of this variability. Therefore, careful consideration should be given when assessing visual prognosis in foveal hypoplasia using optical coherence tomography.     

Chiasmal misrouting and foveal hypoplasia without albinism

BACKGROUND/AIMS: To present the ophthalmological and electrophysiological characteristics of three darkly pigmented, female patients with misrouting and foveal hypoplasia. One of the patients had primary ciliary dyskinesia and situs inversus totalis (Kartagener syndrome). METHODS: Fundus photographs were taken and the angles at which the main temporal arterial branches leave the optic nerve head (ONH) were analysed. Optical coherence tomography (OCT) was performed through the presumed foveal region. Pattern onset visually evoked potentials (VEPs) (check sizes 60', 40/400 ms) were recorded and the chiasmal coefficient was calculated to detect misrouting. RESULTS: Fundus photography showed normally pigmented fundi with absence of the usual foveal hyperpigmentation, foveal avascular zone, and macular and foveal reflexes. On OCT no foveal pit was found. The VEP recordings showed the largest positive CI component over the right hemisphere for the left eye, and over the left hemisphere for the right eye, with the CI almost absent over the ipsilateral hemispheres. The differential derivations showed opposite polarity for the recordings of the two eyes. The chiasmal coefficients of all three patients were significantly indicative of misrouting (-0.99, -0.91, and -0.99, respectively). CONCLUSION: Based on the investigations in these patients the authors propose the hypothesis that foveal hypoplasia and misrouting exist as a distinct entity, and do not comprise the exclusive hallmark of albinism. The findings suggest that misrouting may exert a retrograde influence on foveal development.     

Ultrasound biomicroscopic findings in aniridia

PURPOSE: To describe the ultrasound biomicroscopic features of eyes with aniridia. DESIGN: Observational case series. METHODS: Nineteen eyes of 10 patients with aniridia (six males and four females) ranging in age from 3 months to 53 years (21.0 +/- 16.4, mean +/- SD), and 50 normal subjects (30 men and 20 women) ranging from 16 to 56 years (31.1 +/- 13.2) were evaluated. Ultrasound biomicroscopic findings were recorded in the 3-, 6-, 9-, and 12-o'clock directions. Adult patients (aged 16 years or older) with aniridia were compared with the age-matched controls. RESULTS: Ultrasound biomicroscopy (UBM) detected extremely tiny irises in all eyes with aniridia. The eyes with aniridia showed significantly smaller values than the controls in ciliary body length (4.49 +/- 0.63 versus 5.79 +/- 0.44 mm, P <.001, unpaired Student t test), ciliary body thickness (0.75 +/- 0.17 versus 1.24 +/- 0.22 mm, P <.001), iris root thickness (0.47 +/- 0.14 versus 0.61 +/- 0.07 mm, P <.001), scleral-ciliary process angle (31.7 +/- 3.26 versus 43.1 +/- 4.48 degree, P <.001), and anterior chamber depth (1.99 +/- 0.43 versus 2.94 +/- 0.34 mm, P <.001). In the aniridia eyes, there was a significantly positive correlation between iris thickness and ciliary body thickness (Pearson r = 0.829, P =.001). CONCLUSION: Ultrasound biomicroscopic imaging demonstrated that not only iris hypoplasia but also ciliary body hypoplasia exist in aniridia. Anterior inclination of the ciliary process was also found, which was thought to be at least partly responsible for the shallow anterior chamber.     

Black diaphragm aniridia intraocular lens for congenital aniridia: long-term follow-up

PURPOSE: To present long-term results of implantation of a black diaphragm aniridia intraocular lens (IOL) in eyes with congenital aniridia. SETTING: Eye Hospital, Heinrich-Heine-University, Düsseldorf, Germany. METHODS: Cataract surgery was performed in 19 eyes of 14 patients with congenital aniridia. The black diaphragm aniridia IOL was implanted in front of the capsular bag in the ciliary sulcus. Mean patient age was 30 years (range 10 to 59 years) and mean follow-up, 46 months (range 12 to 84 months). Before surgery, corneal epithelial disorders; corneal pannus; cataract; hypoplasia of the macula, optic nerve, or both; and nystagmus were present in all 19 eyes. Clinically detectable glaucoma was present in 5 eyes. RESULTS: Despite the presence of amblyopia and nystagmus, visual acuity improved in 14 of the 19 eyes. The main postoperative problems were glaucoma deterioration (4 of 19 eyes) or development (4 of 19 eyes), cystoid macular edema (2 of 11 eyes), chronic endothelial cell loss (3 of 11 eyes), and progression of corneal epithelial disorders (4 of 19 eyes). Glaucoma was controlled by medical or surgical therapy in all patients. Intraocular lens explantation was performed in 2 eyes with glaucoma. CONCLUSION: Implantation of the black diaphragm aniridia IOL improved visual acuity in the majority of patients with a variety of endogenous problems in addition to aniridia.     

Outcomes of Boston keratoprosthesis in aniridia: a retrospective multicenter study

PURPOSE: To evaluate the long-term outcomes of keratoprosthesis as an alternative surgical procedure in the management of aniridic keratopathy. DESIGN: Retrospective, multicenter case series. METHODS: Fifteen adult patients (16 eyes) with aniridia who were deemed at high risk for regular donor corneal transplantation underwent a Boston type I keratoprosthesis procedure for visual rehabilitation. Device retention rate, preoperative and postoperative visual acuity, and intraoperative and postoperative complications were studied. RESULTS: The mean age of the patients was 45 (median 50) years. Six of the patients were females. Eleven patients had previously undergone donor corneal transplantations (average two grafts), with failure. In 10 patients, the keratoprosthesis surgery was combined with other procedures such as cataract extraction, tube shunt implantation, vitrectomy, and intraocular lens removal. No intraoperative complications were encountered. The follow-up ranged from two months to 85 months, with a median of 17 months. All devices remained in situ throughout the entire follow-up period. The visual acuity improved in all but one patient from a median of counting fingers (light perception to 20/300) to 20/200 (hand motions to 20/60). Comorbid preoperative conditions particularly optic nerve and foveal hypoplasia limited the final postoperative vision. No endophthalmitis or extrusion of the device occurred. One device required repair procedure without necessitating a removal. CONCLUSIONS: Keratoprosthesis offers significant vision benefits in this patient group.     

ABNORMALITIES OF ERG IN CONGENITAL ANIRIDIA

Congenital aniridia is generally associated with nystagmus, corneal pannus, cataract, ectopia lentis, glaucoma, macular hypoplasia, optic nerve hypoplasia and compromised visual function. Many theories have been proposed, including a failure in the development of the neural ectoderm and/or an aberrant development of mesoderm. We observed the ERG from 19 patients with congenital aniridia. Fourteen patients had abnormal ERG, including the reduced a wave trough under dark adapted red stimuli with dark adap...     

Optical coherence tomography is helpful in the diagnosis of foveal hypoplasia

Purpose: To investigate whether optical coherence tomography (OCT) is helpful in the diagnosis of foveal hypoplasia in children. Methods: Children with albinism and aniridia were examined with Stratus OCT 3 software 4.0.1 (Carl Zeiss Meditec, Dublin, California, USA). A qualitative examination of the macular area was performed with a 128 A‐scans/second‐single‐scan. Macular thickness was measured quantitatively with an automatic fast macular map protocol. The average thickness/volume of the macula was presented as numerical values and as a false colour code in nine modified early treatment of diabetic retinopathy study (ETDRS) areas (A1–A9). A previously collected control group of children was used for comparison. Results: Macular thickness in 13 children with albinism and three children with aniridia was measured with OCT. Comparison with healthy children in the same population was performed. Patients with albinism and aniridia had significantly thicker central macula (A1) and foveola than children in the control group. Conclusion: OCT was found to be useful in the diagnosis of foveal hypoplasia in children.     

The brightness-sense comparison in patients with optic nerve hypoplasia.

The brightness-sense has been assessed for a cohort of individuals with optic nerve hypoplasia, and for a group of normal subjects. It was found to be significantly impaired in the worst eye as compared to the fellow eye in patients with asymmetrical bilateral optic nerve hypoplasia. No difference in brightness between the two eyes was perceived in two patients with segmental optic nerve hypoplasia. The brightness-sense comparison test has not hitherto been applied to patients with optic nerve hypoplasia. The test is simple to use and provides an additional investigative tool for the clinician to detect optic nerve dysfunction.     

Clinical features of Korean patients with congenital aniridia

Purpose

To investigate the clinical features of Korean patients with congenital aniridia.

Methods

This retrospective study focused on 60 eyes from 31 patients who were diagnosed with congenital aniridia at Kangnam St. Mary''s Hospital from 1996 to 2007. Patient age, gender, visual acuity (VA), family history, and previous ocular history were recorded. The presence of keratopathy, glaucoma, cataract, foveal hypoplasia, and other ocular or systemic anomalies were evaluated for each patient.

Results

The proportion of sporadic cases was 29.0%. Cataract (82.5%), glaucoma (51.6%), keratopathy (71.6%), and foveal hypoplasia (81.8%) commonly accompanied aniridia. Thirty-four (60.7%) eyes had VAs less than 20/200 and 20 eyes (35.7%) had VAs between 20/200 and 20/60. In patients without a past history of ocular surgery, the mean central corneal thickness was 643.05 ± 37.67 µm and the mean endothelial cell count was 3,349.44 ± 408.17 cells/mm². Ocular surface surgeries were performed in 6 eyes. The clarity of the transplanted corneal graft vanished in 5 eyes with the progression of peripheral neovascularization and subepithelial fibrosis. The mean age of cataract surgery in 8 eyes was 29.8 ± 5.9 years. Postoperative worsening of corneal clouding and glaucomatous damage were observed in 4 eyes. Two infants had bilateral congenital glaucoma. Two children with sporadic aniridia were identified to have Wilm''s tumors.

Conclusions

Congenital aniridia is a progressive congenital disorder that is commonly accompanied by complications that can lead to impaired vision. Regular, careful examinations for these accompanying complications should be performed in all patients with congenital aniridia.     

Position of the fovea centralis with respect to the optic nerve head.

Examination of the ocular fundus via indirect ophthalmoscopy gives the clinician an impression of foveal position relative to the nerve head. In some patients, the fovea appears to be in an unusual position (i.e., ectopic): it may appear to be higher or lower than expected, or closer to or farther from the nerve head. There is little published quantitative information on this subject. The purpose of this study was to examine foveal position in a group of normal adult eyes, so that clinicians and other researchers will be able to determine on a more objective basis whether or not a given patient shows foveal ectopia. Using ocular fundus photographs for 446 normal adult eyes, we found the foveal center to be, on average, 6.11 degrees +/- 3.32 degrees below a horizontal line bisecting the nerve head. For a smaller sample of 66 eyes, we found the average distance between the nerve head and foveal centers to be 4.93 +/- 0.33 mm (right eye) and 4.88 +/- 0.36 mm (left eye). Correlations of these data for right and left eyes are also examined. Nerve head data for the group of 66 right eyes were also analyzed to yield dimensions of a best-fitting ellipse: the mean minor axis was 1.75 +/- 0.2 mm; the mean major axis 1.95 +/- 0.2 mm. Ectopia (heterotopia) of the fovea has been found in association with chorioretinitis, fibrous traction bands, and/or colobomas of the choroid and optic nerve (including anomalous insertion of the optic nerve), microcephalus, and microphthalmia. A number of separate cases with anomalous nerve heads and/or foveal positions are discussed in this paper.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of 180 patients with sensory defect nystagmus (SDN) and congenital idiopathic nystagmus (CIN)

AIM: Analysis of the diseases underlying congenital nystagmus in a series of patients registered during 6 years as a prerequisite for adequate counselling of the families. PATIENTS AND METHODS: Retrospective study of all patients that presented between 1992 and 1998 with congenital nystagmus not related to visual deprivation or acquired pathologies of the visual pathways. The patients were examined clinically and in dependence on the findings also by electrophysiological (Ganzfeld ERG and VEP, Albino-flash-VEP), psychophysical (colour vision, dark adaptation, spectral sensitivity), and molecular genetic methods. When estimated necessary, family members affected by history and unaffected family members were also examined. In cases of complex neuroophthalmological diseases a neuropaediatric examination including neuroimaging was initiated. RESULTS: In total, 180 patients could be analysed. A sensory defect nystagmus (SDN) was present in 142 patients (79%). The diagnoses were as follows: albinism (any form) in 56 patients (30%), progressive photoreceptor dystrophy in 20 patients (11%), stationary cone dysfunction in 18 patients (10%), bilateral optic nerve hypoplasia in 15 patients (8%), chorioretinal or optic nerve colobomata in 10 patients (6%), aniridia and its variants in 10 patients (6%), familial isolated nystagmus in 8 patients (5%), and congenital stationary night blindness in 5 patients (3%). 38 patients (21%) could not (yet) be classified. DISCUSSION: The prevalence of SDN as the manifesting symptom of a variety of well defined diseases in the present series of at least 79% is similar to that of 90% reported earlier. The precise diagnosis is a prerequisite for counselling the families as to functional prognosis and recurrence risk. Unnecessary neurological examinations including neuroimaging can be avoided.     

Hereditary foveal hypoplasia - clinical differentiation

BACKGROUND: In a family cataract, esotropia and foveal hypoplasia is dominantly transmitted. PATIENTS AND METHOD: Besides the physical examination visual evoked potentials and PAX6 mutation analysis were performed on five of six affected persons and on two who were not. RESULTS: A man of the first generation, deceased before this study, was known to have low vision. His two daughters and their children and grandchildren suffer from cataract, esotropia and foveal hypoplasia. In two cases accompanied by aniridia and atypical iris coloboma respectively. The best visual acuity is 0.5. The VEPs taken of three of the affected people were normal. The PAX6 mutation analysis demonstrated a T to A translocation in the Intron 8 at the position + 2 (= IVS8 + 2T --> A). CONCLUSION: 1) This study confirms that foveal hypoplasia in the so-called isolated form have a similar origin as in aniridia namely PAX6 mutation and that it is a symptom in all cases while the iris anomaly may be variable. 2) In contrast to this foveal hypoplasia in albinism may occur variably in a family while the asymmetry of VEP is a constant finding. 3) Therefore the VEP alone is helpful to differentiate clinically wether a foveal hypoplasia belongs to the albino or to the aniridia group.     

土家族中一个先天性无虹膜家系的临床特点和PAX6基因突变位点分析

目的：确认土家族中一个先天性无虹膜家系的PAX6基因致病突变并分析其临床特点。方法：实验研究。详细询问家族病史并对该家系中所有7 例成员（4 例患者,3 例正常人）进行详细的眼部检查,采集家系成员及100例（50例土家族人和50例汉族人）正常对照者的外周静脉血,提取DNA;对先证者PAX6基因的全部外显子进行PCR扩增及测序;对家系中所有成员和正常对照者进行PAX6基因突变位点的验证检测。结果：该家系中患者主要以虹膜缺损、白内障、眼球震颤、黄斑中心凹发育不良和角膜病变为主要临床表现,虹膜缺损轻重不一,角膜病变和白内障情况随年龄增加而加重。该家系的4 例患者均在第3 外显子与内含子3 交界处出现一个杂合突变（c.357+1G > A）,正常家系成员及正常对照者均无此突变。结论：该先天性无虹膜家系患者虹膜缺损程度不一。PAX6是该家系的致病基因,该家系患者PAX6基因的突变位点是杂合突变(c.357+1G > A）。     

RetCam image analysis of optic disc morphology in premature infants and its relation to ischaemic brain injury

AIMS: To assess optic disc characteristics in premature infants with and without ischaemic brain injury and to evaluate the role of optic disc morphology in dating the injury. METHODS: RetCam fundal images, cranial ultrasounds and magnetic resonance imaging (MRI) of 109 premature infants were analysed. The study cohort was divided into subgroups depending on the presence or absence of periventricular leucomalacia (PVL) and intraventricular haemorrhage (IVH). The control group consisted of infants with normal neuroimaging at term and 2 years of age. Using the image analysis software of the RetCam, optic disc diameter (ODD), optic disc area (ODA), and optic cup area (OCA) were measured at 33-34 weeks gestational age. As serial cranial ultrasonography had been performed, it was possible to date the brain injury in those infants with periventricular white matter (PVWM) damage. RESULTS: Although there was a trend towards reducing ODD, ODA, and OCA with increasing severity of IVH, only the IVH 4 group differed significantly from the controls for these parameters (p = 0.002, p = 0.02, and p = 0.04, respectively). 44.4% of infants with grade 4 IVH had small discs. Only one patient had a large cup in a normal sized disc; this patient had IVH 4. In patients with PVWM damage, the median time of insult was 27 weeks in those with small discs and 28 weeks in those with normal discs. This difference was not significant (p = 0.23). CONCLUSIONS: Premature infants with IVH 4 have an increased incidence of optic nerve hypoplasia. We found no association between disc morphology and timing of brain injury.     

Introduction to genetics in ophthalmology, value of family studies

This paper reviews the author's personal experience with genetic eye diseases and discusses the significance of family studies in providing key information for the advancement of molecular research. Choroideremia: This disease has long been known as an X-linked progressive tapetoretinal degeneration, but it was first described in Japan in 1974 after finding asymptomatic fundus changes in heterozygous female carriers that are compatible with X chromosomal inactivation. Mutations in the disease-causing gene (REP-1) provide a clue to the diagnosis and pathophysiology of the disease.Leber's Hereditary Optic Neuropathy: The clinical expression is so variable among affected individuals and families that mild optic nerve disease of insidious onset should be differentiated from autosomal dominant optic atrophy. Molecular assessment of mitochondrial DNA leads to a definite diagnosis of the disease, but mitochondrial DNA mutations do not fully account for the clinical manifestation and phenotypic variability of the disease.Norrie Disease: This rare X-linked vitreoretinal dysplasia, characterized by congenital bilateral blindness, was documented in Japan some twenty years ago and the disease has been identified in four unrelated Japanese families. The disease, once diagnosed on the basis of elaborate clinical and familial studies, can now be defined by molecular assessment of the Norrie disease gene.Congenital Nystagmus: A four-generation family was described which presented with autosomal dominantly inherited congenital nystagmus, peripheral corneal opacity, and foveal hypoplasia without any iris tissue malformation. The diagnosis of this family was established by detection of a missense mutation in the paired domain of the PAX 6 gene, hence conforming to a forme fruste of congenital aniridia.Sorsby's Fundus Dystrophy: Two Japanese families with Sorsby's fundus dystrophy showed late-onset retinal dystrophy characterized by submacular hemorrhage and atrophy. Our patients presented with visual loss as late as 50 years of age or older due to macula-confined degenerative changes that were similar in all respects to exudative age-related macular degeneration and showed a novel mutation in the tissue inhibitor of the metalloproteinases-3 gene.Age-Related Macular Degeneration (ARMD): We have studied whether there is any association of candidate polymorphic genes involving xenobiotic or antioxidant metabolism with susceptibility to ARMD. Preliminary results suggest that the genetic polymorphism of microsomal epoxide hydrolase is related to potential risk of ARMD.     

Acuity development in infantile nystagmus

PURPOSE: To compare development of acuity in patients with isolated infantile nystagmus and infantile nystagmus associated with a visual sensory defect. METHODS: Visual acuities in 57 children (1 month to 4 years of age) with infantile nystagmus were assessed by using Teller acuity cards oriented vertically during binocular viewing. Twenty-two had isolated infantile nystagmus, 21 had albinism, 7 had aniridia, and 7 had mild or moderate bilateral optic nerve hypoplasia (BONH). Longitudinal acuity was measured in 40 of these patients (mean 1.8, 2.3, 3.1, and 3.3, measurements per patient group, respectively). The rate of acuity development across the study groups was quantified by linear regression of log acuity versus log age and compared to published normative data. RESULTS: The rate of acuity development was similar across all groups and paralleled the normative data. The slope of log grating acuity versus log age (+/-SEM) was normal, 0.73; isolated infantile nystagmus, 0.80 +/- 0.11; albinism, 0.80 +/- 0.11; aniridia, 0.87 +/- 0.16; and BONH, 0.79 +/- 0.18. The slopes were not significantly different (ANCOVA, F(4,142) = 0.21, P = 0.93). Compared with published binocular normative data, mean acuity adjusted for age was reduced by 1.2 octaves in isolated infantile nystagmus and by 1.7 to 2.5 octaves in nystagmus with associated sensory defect. CONCLUSIONS: The rate of acuity development in infantile nystagmus is largely independent of the gaze-holding instability or an associated visual sensory defect. Reduction of mean acuity in albinism, aniridia, and BONH is due to the visual sensory defect and exceeds the acuity reduction observed in isolated infantile nystagmus.