Ocular Fundus Lesions Research Articles

Optical coherence tomography and angiography features of pigmented ocular fundus lesions in hereditary colonic polyposis syndrome.

Optical coherence tomography and angiography features of pigmented ocular fundus lesions in hereditary colonic polyposis syndrome.

Macular Bruch's membrane defects and other myopic lesions in high myopia.

To compare the ocular fundus features of highly myopic eyes with and without macular Bruch's membrane (BM) defects and investigate the associations between macular BM defects and other myopic lesions. This retrospective, observational case series included 262 eyes (139 patients) with high myopia (HM) refractive error ≥-6.0 diopters (D) or axial length ≥26.5 mm from March 2019 to December 2019. The patients underwent a comprehensive ophthalmic examination, including swept-source optical coherence tomography (SS-OCT). The features of macular BM defects and other ocular fundus lesions were examined in OCT images. Totally 51 eyes (19.5%) were detected with macular BM defects, which were characterized by a lack of BM, retinal pigment epithelium (RPE), and an almost complete loss of photoreceptors or choriocapillaris. Eyes with macular BM defects had worse best-corrected visual acuity (BCVA) than those without (P<0.001). Dome-shaped macula (DSM, P=0.042), retinal cysts (P=0.006), choroidal neovascularization (CNV, P<0.001), choroidal defects and abnormality (P=0.003), scleral defects (P=0.015), scleral deformation (P=0.005), posterior staphyloma (P=0.011), and perforating vessels (P<0.001) occurred more frequently in eyes with macular BM defects. In multivariate analysis, the presence of macular BM defects remained the significant association with presence of DSM (P=0.013), scleral defects (P=0.015), posterior staphyloma (P=0.001), perforating vessels (P<0.001) and CNV (P=0.004). Macular BM defects has a prevalence of approximately 20% in HM and it has tight association with other myopic fundus lesions. BM might be crucial in the pathogenesis of myopic fundus lesions due to its biomechanical function. A comprehensive understanding of BM's role is useful for further researches about myopic lesions.

Pigmented Lesions of Ocular Fundus: Clinical Aspects

Pigmented Lesions of Ocular Fundus: Clinical Aspects

Diplopia as presenting sign of Turcot syndrome

PurposeTo describe a patient with diplopia who was diagnosed with Turcot syndrome.MethodsA 10‐year old boy presented with a history of left‐sided sixth and seventh nerve palsy. He underwent imaging of the brain and colon, full ophthalmologic and genetic work‐up.ResultsA 10‐year old boy was referred with combined left‐sided sixth and seventh nerve palsy since one month without symptoms of raised intracranial pressure. BCVA was 6/6 in both eyes. Fundoscopy revealed bilateral, multiple, oval pigmented ocular fundus lesions (POFLs) in the 4 quadrants. These POFLs, together with the cranial nerve palsies raised the suspicion of Turcot syndrome, a familial neoplasia syndrome characterised by familial adenomatous polyposis and tumours of the central nervous system. Urgent MRI scan of the brain and stereotactic biopsy showed a primitive neuroectodermal tumour (PNET) at the pons. Coloscopy revealed multiple polyps. DNA analysis of the APC gene confirmed the clinical diagnosis of Turcot syndrome. The PNET was treated with combined radio‐ and chemotherapy. The patient underwent a prophylactic total colectomy as virtually all patients develop a carcinoma of the colorecal region if left untreated.ConclusionsDiplopia in childhood is rare and seldom innocuous. It requires a prompt and thorough diagnostic evaluation. The presence of POFLs should alert the clinician to the possiblility of Turcot syndrome. Recognition of this rare syndrome can lead to earlier diagnosis, which is vital to appropriate surveillance and early surgical intervention of the highly frequent neoplasias in Turcot Sydrome.

A potential life-saving diagnosis—recognizing Turcot syndrome

A previously healthy 9-year-old girl presented with ataxia, headaches, and nausea of 1 month's duration. Magnetic resonance imaging demonstrated a large posterior fossa mass. Posterior segment examination revealed pigmented ocular fundus lesions (POFLs), which included cometoid dark lesions with depigmented tails and smaller, dark midperipheral lesions. The patient underwent resection for a medulloblastoma. Because of these specific retinal lesions in combination with her medullobastoma, a diagnosis of Turcot syndrome was made and subsequently confirmed by genetic testing. Turcot syndrome is one of the familial adenomatous polyposis (FAP) syndromes. This diagnosis may be life-saving because 100% of FAP patients develop colon cancer that can be cured only early with timely colectomy.

Pigmented Ocular Fundus Lesions in a 6-Year-Old Girl

Pigmented Ocular Fundus Lesions in a 6-Year-Old Girl

An interesting case of "bear track dystrophy"

Bear track dystrophy, is a rare condition, which forms part of the disorder known as the grouped congenital hypertrophy of the retinal pigment epithelium (CHRPE), a peculiar congenital anomaly of the retinal pigment epithelium diagnosed by its characteristic ophthalmoscopic appearance. This disorder is usually without any functional consequence with patients typically having a normal vision, color vision, normal visual fields, dark adaptation, electroretinography, and electrooculography findings. The main differential diagnosis of CHRPE includes choroidal naevus, choroidal melanoma, chorioretinal scar, subretinal hematoma, pigmented epiretinal membrane, and reactive retinal pigment epithelial hyperplasia. Since CHRPE, in itself is a totally benign condition with no associated ocular or systemic complications, it becomes that much more important to distinguish it from the more serious vision/life-threatening conditions like choroidal melanoma as well as from the other pigmented ocular fundus lesions associated with familial cancer syndromes like familial adenomatous polyposis.

Cancer and the eye: giant steps forward. The Cambridge Symposium 2012

Cancer and the eye: giant steps forward. The Cambridge Symposium 2012

Pigmented and depigmented lesions of the ocular fundus

Pigmented and depigmented ocular fundus lesions (de-POFLs) can be isolated and clinically insignificant, or they may be the hallmark of associated serious systemic disorders such as familial polyposis. The ophthalmologist is often called upon to look for these retinal lesions, or may encounter them in the course of routine examination when appropriate medical referral becomes essential. The ophthalmoscopic and location differences between grouped pigmentation of the retinal pigment epithelium (bear tracks) and multiple POFLs associated with familial adenomatous polyposis is reviewed. The differential diagnosis, morphology and associations of de-POFLs are also listed and some of the associated genetic conditions are reviewed. Familiarity with the morphologic and ophthalmoscopic features of pigmented and de-POFLs is essential for the ophthalmologist so that an exact diagnosis is made and the appropriate workup and referrals initiated.

Ocular Manifestations of Familial Adenomatous Polyposis (Gardner Syndrome)

Familial adenomatous polyposis (FAP) is a colon cancer predisposition syndrome in which hundreds to thousands of precancerous colonic polyp become evident at a mean age of 16 years (range, 7-36 years). By age 35 years, 95% of patients have polyps. Gardner syndrome is the eponym given to a subgroup of FAP with extracolonic manifestations, such as pigmented ocular fundus lesions that resemble congenital hypertrophy of the retinal pigment epithelium, among others.

Clinical management and genetics of gastrointestinal polyps in children.

Clinical management and genetics of gastrointestinal polyps in children.

Late ophthalmological complications after total body irradiation in non-human primates

Purpose : To investigate the long-term eff ects of total body irradiation (TBI) on the incidence and time course of ocular complications. Materials and methods : Rhesus monkeys treated with TBI photon doses up to 8.5Gy and proton doses up to 7.5Gy were studied at intervals up to 25 years post-irradiation. They were compared with control groups with a similar age distribution. Cataract formation and ocular fundus lesions were scored according to a standardized protocol. Fluorescein angiography and histopathology was performed in selected animals. Results : Cataract formation occurred after a latent period of 3-5 years. Significant cataract induction was observed for photondoses of 8 and 8.5Gy and beyond 20 years after proton irradiation. The severity of the lesions represents significant impairment of vision and would require cataract surgery if similar results occurred in human bone marrow transplant patients. Fluorescein angiography demonstrated a normal pattern of retinal vessels in 13 out of 14 animals (93%) from the irradiated group and in eight out of nine animals (89%) from the control group. No additional lesions apart from age-related degenerative changes could be demonstrated. Histological evaluation revealed no radiation-associated vasculopathy. Conclusions : Radiation alone for doses up to 8.5Gy of photons does not carry a potential risk for fundus pathology, whereas clinically important cataract induction should be anticipated within 5 years after photon doses of 8.0 and 8.5Gy and proton doses in excess of 2.5Gy.

APC gene mutations and extraintestinal phenotype of familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is caused by germline mutation of the adenomatous polyposis coli (APC) gene on chromosome 5q. This study assessed genotype-phenotype correlations for extraintestinal lesions in FAP. Mutations of the APC gene were compared with the occurrence of seven extraintestinal manifestations in 475 FAP patients from 51 families. The frequency of manifestations was adjusted for different ages of patients using person years of exposure. In pedigrees without identified APC gene mutation, analysis of linkage to chromosome 5q and/or assessment of neoplasms for replication errors characteristic of mutation in mismatch repair genes were performed. FAP patients from the 42 families (82%) with identified mutations of the APC gene had more frequent expression of extraintestinal manifestations than affected individuals without identified mutations (risk ratio 1.2-4.0; significant difference for cutaneous cysts). The presence of a cutaneous cyst or extraintestinal cancer significantly increased the likelihood of detection of a mutation in the APC gene (94% and 92% respectively; p < 0.05). In patients without identified APC gene mutation, linkage to the APC gene was found in one large family (lod = 5.1, theta 0.01), and replication error phenotype was absent in all 24 neoplasms from 16 members of these nine pedigrees. Expression of pigmented ocular fundus lesions was strongly associated with mutations in codons 541-1309, but no other extraintestinal manifestations were related to mutation position. Multiplicity of extraintestinal manifestations was high with mutation in codons 1465, 1546, and 2621. Patients with the colorectal phenotype of FAP but no extraintestinal manifestations may have non-truncating mutations of the APC gene or mutation in a gene other than APC or mismatch repair genes. The site of APC gene mutation is associated with pigmented ocular fundus lesions (codons 542-1309) and predisposition to multiplicity of extraintestinal manifestations (codons 1465, 1546, and 2621).

Characterization of two novel adenomatous polyposis coli (APC) gene mutations in patients with familial adenomatous polyposis (FAP)

Patients with Familial Adenomatous Polyposis (FAP) manifest numerous colorectal adenomas as well as benign and malignant extra-colonic lesions. Adenomatous polyposis coli (APC) gene mutations are the underlying genetic defect in FAP. We analyzed germline DNA of 81 unrelated FAP patients and evaluated correlation of APC mutation genotype and clinical phenotype. Germline APC mutations were identified in 18 FAP patients including two novel 2 bp deletions at APC codons 1067 and 1259. FAP patients were screened for hypertrophic ocular fundus lesions, desmoids and peri-ampullary adenomas. As reported previously (Olshwang et al 1993b), a positive correlation for the frequency of retinal lesions and germline APC mutation was observed among all FAP patients except one. No significant correlation was observed for APC mutation genotype and the occurrence of desmoids and peri-ampullary adenomas. Genetic factors contributing to familial segregation of these lesions need further investigation.

Gardner syndrome: study and follow-up of a family.

A study is in progress of a family (Family P) with Gardner syndrome (familial adenomatous polyposis with extraintestinal manifestations-FAPG). Occult bone lesions of the jaws and ocular fundus lesions were found in a number of affected and at-risk relatives. In some, these "markers" were found early in life before the appearance of colonic polyps. Family P is remarkable for differences in expression of the gene manifested by differences in the age-at-onset of polyps of the colon, in number and size of polyps, and in occurrence of desmoids. These differences may explain why some at-risk relatives wisely followed medical surveillance plans while others, who lacked symptoms, failed to do so. Others without medical guidance undertook their own independent "treatment." As knowledge about extracolonic lesions has increased and surgical treatment for FAPG improved from the time the first affected member of Family P received her diagnosis in 1953, the outlook for survival has also improved. Family communication and that among professionals treating families with FAPG may be improved as worldwide Polyposis Registries increase in number. The risk of postsurgical extraintestinal complications is reason enough to urge life-long medical surveillance for all at-risk relatives.

Value of combined phenotypic markers in identifying inheritance of familial adenomatous polyposis.

Familial adenomatous polyposis is an autosomal dominant disease characterised by the development of hundreds of colorectal adenomas in young adults. Occult radio-opaque jaw lesions and pigmented ocular fundus lesions (formerly called congenital hypertrophy of the retinal pigment epithelium) are extraintestinal phenotypic markers for this disorder. We evaluated the usefulness of the combination of these markers for identifying patients who have inherited familial adenomatous polyposis. Forty three affected patients and 12 unaffected first degree relatives from 24 families with familial adenomatous polyposis, including four families without extraintestinal manifestations, were examined for both phenotypic markers. Thirty three of the 43 patients (77%) with familial adenomatous polyposis were positive for both markers, including patients from two families without extraintestinal manifestations. By contrast, only one of 12 (8%) unaffected first degree relatives over 35 years of age had both markers. The sensitivity of the combination of these markers in identifying patients who inherited familial adenomatous polyposis was 77%, the specificity 92%, the predictive value of a positive test 97%, the predictive value of a negative test 52%, and the efficacy 80%. The combined markers had improved efficacy over either marker alone (70% for occult radio-opaque jaw lesions and 67% for pigmented ocular fundus lesions). We conclude that the presence of both occult radio-opaque jaw lesions and pigmented ocular fundus lesions in a person at risk indicates a high probability of inheritance and expression of familial adenomatous polyposis.

Waardenburg I syndrome: A clinical and genetic study of two large Brazilian kindreds, and literature review

Two large kindreds with Waardenburg I syndrome are described. The total number of affected individuals is 73. The major manifestations are telecanthus (the only constant anomaly in all cases), prominent nasal root, round or square tip of nose, hypoplastic alae, smooth philtrum, bushy eyebrows with synophrys, sensorineural deafness, heterochromia or hypoisochromia iridis, hypopigmented ocular fundus, white forelock, premature greying, and hypopigmented skin lesions. These and other aspects of the syndrome, associated findings, frequency, genetic heterogeneity, pathogenesis, animal models, and gene linkage and mapping are reviewed briefly.

Pigmented Ocular Fundus Lesions in the Inherited Gastrointestinal Polyposis Syndromes and in Hereditary Nonpolyposis Colorectal Cancer

The authors studied pigmented ocular fundus lesions in three different forms of hereditary gastrointestinal polyposis and in hereditary nonpolyposis colorectal cancer. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) was present in at least one member of 23 families with Gardner's syndrome. By contrast, CHRPE was not found in three families with familial polyposis coli, four families with hereditary nonpolyposis colorectal cancer, and three families with Peutz-Jeghers syndrome. Pigmented ocular fundus lesions of the CHRPE-type appear to be specific to Gardner's syndrome among inherited diseases with gastrointestinal polyposis.

Hepatoblastoma, pigmented ocular fundus lesions and jaw lesions in Gardner syndrome.

Hepatoblastoma is a rare neoplasm of infants and children only recently documented in association with hereditary adenomatous polyposis of the colon [Kingston et al., 1983]. We report four children with hepatoblastoma from four unrelated families with Gardner syndrome (GS). One child, now 19 years old, survived after a resection of a hepatoblastoma in infancy and recently was found to have GS. He has an associated odontoma and pigmented ocular fundus lesions, both of which have been shown to be clinical markers of GS. Many individuals in these four GS families, both affected and at risk, have osteomatous jaw lesions and pigmented ocular fundus lesions. A search for colonic polyps should be made in families of infants and children with hepatoblastoma. If the child survives, he or she should be monitored for the later appearance of colonic polyps. The finding of jaw lesions and/or pigmented ocular fundus lesions in relatives at risk are indications of the possible presence of the GS gene.

Prevalence and importance of pigmented ocular fundus lesions in Gardner's syndrome.

We examined 134 members of 16 families with Gardner's syndrome for pigmented ocular fundus lesions. Of 41 patients with documented Gardner's syndrome, 37 (90.2 percent) had such lesions. The lesions were bilateral in 32 of the patients (78.1 percent) and in 2 of 42 controls (4.8 percent). Twenty (46.5 percent) of 43 first-degree relatives at 50 percent risk for Gardner's syndrome had bilateral pigmented fundus lesions, indicating that they had probably inherited the abnormal gene. The presence of bilateral lesions, multiple lesions (more than four), or both appeared to be a specific (specificity, 0.952) and sensitive (sensitivity, 0.780) clinical marker for Gardner's syndrome. The lesions are probably congenital; they were observed in a three-month-old baby at risk. The multiplicity of the pigmented fundus lesions and their association with diffuse disturbances of the retinal pigment epithelium in the same eye suggest a widespread expression of the abnormal gene in the retinal pigment epithelial cells.