1: Ophthalmic Genet. 2009 Mar;30(1):54-5. 

LCA5, a rare genetic cause of leber congenital amaurosis in Koreans.

Seong MW, Kim SY, Yu YS, Hwang JM, Kim JY, Park SS.

Department of Laboratory Medicine, National Cancer Center, Goyang, South Korea.

PURPOSE: Leber congenital amaurosis (LCA), the most severe form of inherited
retinal dystrophy, is a genetically heterogenous disorder and more than nine
genes only account for about half of LCA cases. Recently, LCA5 was identified as
a rare genetic cause of LCA. Here, we analyzed the LCA5 gene in 14 LCA patients
with no mutation identified in any other known LCA genes and 3 patients with one
unclassified missense variant in RPGRIP1. METHODS: We analyzed all exons and
flanking regions of the LCA5 gene using direct sequencing. We included 170
control subjects in this study to screen novel sequence variant and analyzed the
functional effect of a missense variant using in-silico prediction. RESULTS: No
pathogenic mutation in LCA5 was found in our seventeen patients including 3
patients with one unclassified missense variant in RPGRIP1. We identified one
novel missense variant, c.1642C>T (p.Pro548Ser), in exon 9. We considered it
benign because it was found in control subjects and predicted not to be harmful
to protein function on in-silico prediction. We identified another intronic
variant, which has been confirmed to be benign through mRNA analysis.
CONCLUSIONS: This result shows that mutation in LCA5 is likely to be a rare
genetic cause in Koreans and suggests that further investigation to identify
other causative genes is necessary in Koreans.

Publication Types:
    Research Support, Non-U.S. Gov\'t

PMID: 19172513 [PubMed - indexed for MEDLINE]

2: Ophthalmic Genet. 2009 Mar;30(1):50-3. 

Cystoid macular edema in a patient with chronic progressive external
ophthalmoplegia with mitochondrial myopathy.

Brubaker JW, Mohney BG, Pulido JS.

Department of Ophthalmology, University of Utah School of Medicine, Salt Lake
City, Utah, USA.

PURPOSE: To report the findings of cystoid macular edema in a patient with
chronic progressive external ophthalmoplegia and other systemic features of
mitochondrial myopathy. DESIGN: Observational case report. METHODS:
Retrospective review of the ophthalmic examination and genetic studies of a
patient with chronic progressive ophthalmoplegia. RESULTS: Fundus photos,
retinal optical coherence tomography, and fluorescein angiography were
significant for findings consistent with bilateral cystoid macular edema, which
were found to have resolved after 18 months without treatment. The medical
examination supported the diagnosis of chronic progressive external
ophthalmoplegia. Fundus photos, retinal optical coherence tomography, and
fluorescein angiography were significant for findings consistent with cystoid
macular edema. CONCLUSIONS: This case demonstrates the occurrence CME in a
patient with CPEO and additional systemic features.

Publication Types:
    Case Reports
    Research Support, Non-U.S. Gov\'t

PMID: 19172512 [PubMed - indexed for MEDLINE]

3: Ophthalmic Genet. 2009 Mar;30(1):45-9. 

Triple A or Allgrove syndrome. A case report with ophthalmic abnormalities and a
novel mutation in the AAAS gene.

Villanueva-Mendoza C, artinez-Guzman O, Rivera-Parra D, Zenteno JC.

Department of Genetics, Asociacion para Evitar la Ceguera en Mexico, Mexico
City, Mexico. villanuevacristina@hotmail.com

PURPOSE: Triple A syndrome is a rare autosomal recessive disease characterized
by achalasia, alacrima, adrenocorticotrophic hormone resistant adrenal failure
and some neurologic abnormalities. We report a nine year old patient with
alacrima, optic atrophy and achalasia with mutation in the AAAS gene. METHODS:
PCR amplification of the complete coding sequence as well as the exon-intron
junctions of AAAS gene was performed in DNA from the patient and his parents.
RESULTS: AAAS gene analysis demonstrated a homozygous A to G mutation at
nucleotide position 122 in exon 1 in DNA from the patient. CONCLUSIONS: The
novel mutation described confirms the diagnosis.

Publication Types:
    Case Reports
    Research Support, Non-U.S. Gov\'t

PMID: 19172511 [PubMed - indexed for MEDLINE]

4: Ophthalmic Genet. 2009 Mar;30(1):40-4. 

Published international classification of retinoblastoma (ICRB) definitions
contain inconsistencies--an analysis of impact.

Novetsky DE, Abramson DH, Kim JW, Dunkel IJ.

Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New
York 10021, USA.

PURPOSE: To determine the impact of subtle differences (most notably in their
classification of group E eyes) in two published versions of the ICRB
(Philadelphia and the Children\'s Hospital Los Angeles). METHODS: Analysis of a
series of 96 eyes with intra-ocular retinoblastoma. RESULTS: The disparate
criteria of the 2 published ICRB schemas affected group assignment of 5.2% of
the eyes (25% of the group E eyes). CONCLUSION: Discrepancies need to be
reconciled to ensure accurate and uniform application of the ICRB.

Publication Types:
    Research Support, Non-U.S. Gov\'t

PMID: 19172510 [PubMed - indexed for MEDLINE]

5: Ophthalmic Genet. 2009 Mar;30(1):37-9. 

Congenital alacrima in a patient with blepharophimosis syndrome.

Athappilly GK, Braverman RS.

The University of Colorado at Denven and Health Services Center, Rocky Mountain
Lions Eye Institute, Denver, CO 80045, USA. geetha.athappily@UCHSC.edu

PURPOSE: To report a case of congenital alacrima in a patient with
Blepharophimosis Syndrome (BPES). METHODS: Case report of a 9-month-old female
who presented with severe dry eyes. Further investigation revealed bilateral
absence of lacrimal glands confirmed by CT. This unique case and its management
are discussed. RESULTS: Conservative management with artificial tears and
ointment did not treat the ocular surface dryness. A combination of aggressive
lubrication with surgical occlusion of the lower lid punctums was required to
improve the corneal surface. CONCLUSION: BPES can be associated with many
ophthalmic and facial abnormalities. Review of the pubmed literature, reveals
this is the first reported case of alacrima and BPES. Patient with alacrima have
severe ocular surface dryness, which requires aggressive and life long
lubrication and tear supplementation.

Publication Types:
    Case Reports

PMID: 19172509 [PubMed - indexed for MEDLINE]

6: Ophthalmic Genet. 2009 Mar;30(1):31-6. 

The effect of therapy refusal against medical advice in retinoblastoma patients
in a setting where treatment delays are common.

Sitorus RS, Moll AC, Suhardjono S, Simangunsong LS, Riono P, Imhof S,
Volker-Dieben HJ.

Department of Ophthalmology, Faculty of Medicine University of Indonesia, Cipto
Mangunkusumo National Hospital, Jakarta, Indonesia. ritasito@yahoo.com

BACKGROUND: Patients who refuse therapy against medical advice may be at risk of
adverse health outcomes. We analyzed the impact of therapy refusal and its
effect on the survival of retinoblastoma patients. PATIENTS AND METHODS: 165
consecutive untreated retinoblastoma patients admitted to the CM-Hospital,
between 1993-2000 were evaluated retrospectively. Survival outcomes and its
association with delays and tumor staging were analyzed using Kaplan-Meier and
Cox-Regression. RESULTS: Of the 165 cases, 78 cases (47,3%) were assigned to the
"No-Refusal-Group"; 52 cases (31,5%) to "Temporary-Refusal-Group," 30 cases
(18,2%) to "Definite-Refusal-Group." Survival rates of patients who temporarily
refused were significantly lower than those who did not refuse the therapy (p <
0.05). Progression of tumor stage was highly associated with temporary-refusal
(p < 0.0005). In the Cox-Regression model, clinical staging of tumor was highly
associated, whereas admission delay and treatment delay were slightly associated
with the overall survival (p < 0.05, adjusted-hazard-ratio 6.321, 1.031,1.025,
respectively). The clinical staging is the strongest variable associated with
patient survival outcome. Delay >or= 6 months between first sign and admission
is highly associated with tumor progression (p < 0.0005). CONCLUSIONS: First,
the high level of therapy refusal in a developing country like Indonesia has an
adverse effect on the survival outcome of retinoblastoma patients. Second, the
change of the tumor stage from intraocular to extraocular is the most adverse
predictive factor for survival. Third, the advanced stage of the tumor is caused
by long delay to admission. In a developing country the parents of many young
patients refuse to accept the recommended therapy and therefore the tumor may
reach a critical stage for the prognosis.

Publication Types:
    Research Support, Non-U.S. Gov\'t

PMID: 19172508 [PubMed - indexed for MEDLINE]

7: Ophthalmic Genet. 2009 Mar;30(1):23-30. 

Phenotypic overlap of familial exudative vitreoretinopathy (FEVR) with
persistent fetal vasculature (PFV) caused by FZD4 mutations in two distinct
pedigrees.

Robitaille JM, Wallace K, Zheng B, Beis MJ, Samuels M, Hoskin-Mott A, Guernsey
DL.

Department of Ophthalmology and Visual Science, Dalhousie University, Halifax,
Nova Scotia, Canada.

PURPOSE: To describe a severe familial exudative vitreoretinopathy (FEVR)
phenotype seen in infancy that resembles persistent fetal vasculature (PFV)
caused by mutations in the FZD4 gene in two pedigrees with high intrafamilial
variability. METHODS: Three infants presented with features compatible with
bilateral PFV. Eye examinations from the affected children and their relatives
were reviewed retrospectively (follow-up:18 months-9 years). Mutation screening
was performed using direct sequencing of the FZD4, LRP5 and NDP genes. RESULTS:
Bilateral retinal folds extending from the optic nerve to the inferotemporal
aspect of the lens mimicing PFV were observed in two of the three affected
children before the age of two months. The third child was examined at birth,
and the avascular peripheral retina treated with diode laser within one week of
age, with subsequent arrest of the disease process. A FZD4 mutation,
M493_W494del, was identified in one affected child in pedigree 1, and a novel
missense mutation, I114T, was detected in 2 affected children in pedigree 2;
while no mutations were found in NDP or LRP5 genes in the 3 affected children.
In both pedigrees, at least one affected relative was asymptomatic and failed to
show the characteristic avascular changes of FEVR. CONCLUSIONS: The clinical
features in the three children and their relatives with a documented FZD4
mutation support the previous reports of a high degree of intrafamilial and
interfamilial variability in FEVR. In extreme cases with very early onset, the
development of a retinal fold can mimic PFV, a non-hereditary condition with
rare exception.

Publication Types:
    Case Reports
    Research Support, Non-U.S. Gov\'t

PMID: 19172507 [PubMed - indexed for MEDLINE]

8: Ophthalmic Genet. 2009 Mar;30(1):19-22. 

Uncommon associations with ataxia-telangiectasia: vitiligo and optic disc
drusen.

Sari A, Okuyaz C, Adiguzel U, Ates NA.

Department of Ophthalmology, Mersin University Medical School, Mersin, Turkey.
docayc@yahoo.com

Ataxia-telangiectasia (A-T) is an autosomal recessive condition presented by
progressive cerebellar ataxia, oculocutaneous telangiectasia, humoral and
cellular immunodeficiencies and a predisposition to malignancy. We report on a
13 years old male patient with the diagnosis of A-T associated with uncommon
clinical features; optic disc drusen and vitiligo. To our knowledge, this is the
first report of A-T associated with these findings.

Publication Types:
    Case Reports

PMID: 19172506 [PubMed - indexed for MEDLINE]

9: Ophthalmic Genet. 2009 Mar;30(1):13-8. 

Lack of association between optineurin gene variants T34T, E50K, M98K,
691_692insAG and R545Q and primary open angle glaucoma in Brazilian patients.

Caixeta-Umbelino C, de Vasconcellos JP, Costa VP, Kasahara N, Della Paolera M,
de Almeida GV, Cohen R, Mandia C Jr, Rocha MN, Richeti F, Longui CA, de Melo MB.

Department of Ophthalmology, Faculty of Medical Sciences, Glaucoma Service,
Irmandade da Santa Casa de Misericordia de Sao Paulo, Sao Paulo, Brazil.

PURPOSE: To verify the frequencies of T34T, E50K, M98K, 691_692insAG, and R545Q
variants in the optineurin (OPTN) gene in Brazilian subjects with primary
open-angle glaucoma (POAG) and controls. PATIENTS AND METHODS: Ninety-nine
patients with POAG and 100 normal controls were enrolled in this study. The
frequency of alterations in the OPTN gene was analyzed by direct sequencing and
enzymatic digestion of PCR products. RESULTS: None of the five alterations
evaluated was significantly associated with POAG when compared to controls.
However, the T34T silent change was present in greater frequency in POAG
patients (37.37% vs. 23.00% in controls), while the R545Q change was more
prevalent in controls (23.00% vs. 10.10% in POAG). The M98K and 691_692insAG
presented with low frequencies in POAG patients (1.01% and 2.02%, respectively)
and controls (2.00% and 2.00%, respectively). The E50K substitution was not
observed. CONCLUSION: Our data show no association between the five evaluated
variants and POAG in the Brazilian population.

Publication Types:
    Research Support, Non-U.S. Gov\'t

PMID: 19172505 [PubMed - indexed for MEDLINE]

10: Ophthalmic Genet. 2009 Mar;30(1):7-12. 

Duane retraction syndrome, nystagmus, retinal pigment epitheliopathy and
epiretinal membrane with micro- and pachygyria, developmental delay, hearing
loss and craniopharyngioma.

D\'Amelio S, Lassen N, Vasiliou V, Bateman JB.

Department of Pediatric Ophthalmology, Ophthalmic Hospital C. Sperino, Turin,
Italy.

PURPOSE: To report the association of Duane syndrome with nystagmus and a
patterned hyperpigmentation of the retinal pigment epithelium, developmental
delay, micro- and pachygyria and craniopharyngioma. CASE REPORT: We describe a
12-year old girl with developmental delay, hearing loss, cortical micro- and
pachygyria, and a cystic craniopharyngioma; her ocular features include
unilateral Duane syndrome, monocular nystagmus under binocular conditions, and a
patterned hyperpigmentation of the retinal pigment epithelium. Her mother had
similar retinal pigment epithelial abnormalities. CONCLUSIONS: The combination
of two neuronal migrational disorders, the unusual retinal pigment epithelial
abnormalities in the proband and her mother, and evidence that each feature may
be genetic and are suggestive of a genetic basis for this constellation of
features.

Publication Types:
    Case Reports

PMID: 19172504 [PubMed - indexed for MEDLINE]

11: Ophthalmic Genet. 2009 Mar;30(1):1-6. 

Macular dysfunction and morphology in spinocerebellar ataxia type 7 (SCA 7).

Hugosson T, Granse L, Ponjavic V, Andreasson S.

Department of Ophthalmology, Central Hospital, Kristianstad, Sweden.
Therese.Hugosson@med.lu.se

PURPOSE: To characterize the clinical phenotype regarding retinal function and
macular appearance in patients with spinocerebellar ataxia type 7 (SCA 7), with
an emphasis on electrophysiological findings. METHODS: Three patients from two
Swedish families were given an ophthalmological examination including visual
acuity, fundus inspection, Farnsworth\'s color vision test, Goldmann perimetry,
full-field electroretinography (full-field ERG), multifocal electroretinography
(mfERG) and optical coherence tomography (OCT). DNA was analyzed with polymerase
chain reaction for CAG trinucleotide expansion repeats in the SCA 7 gene.
RESULTS: Molecular analysis demonstrated abnormally expanded CAG repeats in the
gene for SCA 7, which encodes the protein ataxin-7, thus confirming the
diagnosis SCA 7. In the oldest patient very discreet pigmentary changes in the
maculae were found, but with that exception the patients had a normal
ophthalmoscopic fundus appearance and OCT demonstrated only minor changes. MfERG
indicated predominantly central involvement, especially in the early disease
stages, which in pace with disease progression extended from the center to the
more peripheral areas. Full-field ERG in the oldest patient demonstrated
bilaterally distinctly prolonged 30-Hz flicker implicit time, verifying
widespread cone photoreceptor degeneration. CONCLUSIONS: The patients with
genetically confirmed SCA 7 presented an early macular dysfunction, preceding
any signs of abnormalities in fundus appearance. According to the
electrophysiological findings the primary dysfunction involves the cone
photoreceptors in the foveal region, however in an older patient involvement of
cone photoreceptors throughout the retina was verified. This is in accordance
with the theory that ataxin-7 interacts with CRX transcription, since it is
known that mutations in the CRX gene cause cone-rod dystrophy.

Publication Types:
    Research Support, Non-U.S. Gov\'t

PMID: 19172503 [PubMed - indexed for MEDLINE]