Incomprehensible treatment of retinoblastoma with high doses of vitamin C.

PURPOSES: To inform about a case of neglected retinoblastoma that was left untreated for more than 3 years by parents. During this time period the local finding worsened from endophytic retinoblastoma group B according IIRC (ABC classification) to extraorbital propagation. BACKGROUND: Retinoblastoma is the most common intraocular tumor in childhood, that occurs approximately in 1 : 15-20 000 births worldwide. In European region cases of extraocular propagation are very infrequent. Extraorbital propagation is extremely rare in middle and high income countries. METHODS: We report the preoperative ophthalmological findings, MRI imaging, treatment methods and postoperative results of this case. RESULTS: After initial dose of six courses of chemotherapy patient underwent surgery (orbital exenteration). In postoperative period patient received two more courses of chemotherapy. In spite of progressed stage of the disease, we obtained good results with our therapy. CONCLUSIONS: We suppose that good treatment results, in spite of extraordinary long lag interval and hopeless pretreatment condition, caused by alternative therapy with high doses vitamin C and no protein intake, were caused by therapeutic naïve retinoblastoma with an absence of RB1 gene mutation (Fig. 6, Ref. 7).

Why is it necessary to examine retina when the patient suffers from aplastic anemia?

PURPOSES: To inform about a case of Revesz syndrome (RS) with initial ophthalmological symptomatology of severe proliferative vitreoretinopathy of the left eye (LE). After the aplastic anemia had developed, RS was established. The exudative retinopathy was successfully treated with photocoagulation on the right eye (RE). BACKGROUND: RS is characterized by fatal bone marrow failure, exudative retinopathy, neuroradiographic abnormalities, neurodevelopmental delay and skin abnormalities. Non-treated exudative retinopathy leads to blindness. METHODS: We report ophthalmological findings as follows: fundus photography and fluorescein angiography (FA) acquired by examinations under general anesthesia in patient with RS. Results of genetic tests helped to establish the diagnosis. RESULTS: Two­year old Caucasian male was examined due to total retinal detachment on LE and signs of chorioretinal scarring on RE. In preoperative screening, thrombocytopenia was detected; later, severe pancytopenia developed. Considering the hematological findings and clinical appearance, we suspected RS, which was confirmed by genetic tests. We found a pathogenic mutation in gene TINF2 (variant c.865C>T;p.Pro289Ser) in a mosaic state with autosomal dominant mode of inheritance. This mutation has not been described in RS yet. Blind LE was enucleated because of dolorous neovascular glaucoma. FA of RE shows excessive areas of capillary nonperfusion with vascular abnormalities and exudation. After the photocoagulation, the visual acuity (VA) on RE remains 0.9 at the age of 7 years. CONCLUSIONS: RS is an extremely rare condition.  The initial symptomatology could be ophthalmological or hematological. The positive finding of TINF2 gene mutation helped in establishing the correct diagnosis. The ischemic retinopathy was successfully treated by photocoagulation (Fig. 6, Ref. 6). Text in PDF www.elis.sk.

ß-blockers in the treatment of periocular infantile capillary haemangioma.

Infantile capillary haemangioma (IH) is the most common congenital vascular tumor of childhood and infancy. Although the majority of these lesions regress spontaneously, many of children with IH particularly in the periocular or orbital region need treatment. Ocular indications for treatment include obstruction of the visual axis or high degrees of astigmatism causing amblyopia, exposure keratopathy secondary to proptosis or compressive optic neuropathy. Our purpose was to assess the effectiveness and tolerance of beta-blockers (BB), propranolol and metoprolol, in the treatment of these lesions. We performed a retrospective review of 21 infant patients with periocular or/and orbital IH. The mode of treatment for 13 patients was with the non-selective ß blocker propranolol (PR) and 8 patients were treated with the ß1 selective blocker metoprolol (ME). We analysed the changes in IH lesion size, colour and thickness after the treatment with ß-blockers, the onset and the period of their action, recurrence of IH and adverse effects of the treatment. The effectiveness of metoprolol to propranolol was compared as well as their use in combination with systemic steroids. In the first month of the treatment with beta-blockers, significant regression of the IH was observed in all patients. During the following months of treatment the regression was not rapid and after 6 to 12 months the lesions remained stationary. The final result of the treatment of 15 patients (71.4%) was deemed excellent while the treatment of 5 patients (23.8%) was deemed good. A single patient (4.7%) had only fair response to the therapy. During the whole series no serious life-threatening adverse effects were observed. The usage of beta-blockers, both propranolol and metoprolol, in the therapy of orbital and periocular capillary infantile haemangioma seems to be very effective in reduction of the tumor and had only rare, minimum adverse effects. These facts favour beta-blockers as the first line treatment of children with IH.

Clustering of mutations in the 5' tertile of the NF1 gene in Slovakia patients with optic pathway glioma.

Optic pathway gliomas (OPG) occur in 15% of patients with neurofibromatosis type 1 (NF1; OMIM 162200). Genotype-phenotype correlations in patients with NF1 may help to determine the risk group for developing complications such as OPG in coincidence with other NF1.features. We evaluated 52 patients with NF1 (25 with OPG and 27 without OPG). All subjects underwent a clinical examination focused on neurofibromatosis type 1 and molecular diagnostics of NF1 gene using protocol based on RNA analysis confirming the diagnosis of NF1. In the group with OPG patients, there was a significantly higher incidence of freckling (P=0.017), neurofibromatosis bright objects (NBO) (P=0.0038), compared to the group without OPG. The differences between the groups with respect to Lisch nodules were on the borderline of statistical significance (P=0.088). The frequency of neurofibromas in the group with OPG was not significant (P=0.9). From all patients with the mutation localized in the first tertile of the NF1 gene majority (71%) had optic glioma compared to individuals who didn't have the OPG 29% (P=0.0049). Our results present the clustering of mutations in the 5'tertile of NF1 gene in patients with optic nerve glioma and suggest higher incidence of freckling and neurofibromatosis brain objects in these patients. Molecular analysis of NF1 gene is important part in complex management of NF1 patients and contributes to a better understanding of clinical picture of NF1 patients. .

Use of Corneal Topography in Pediatric Ophthalmology.

AIM: To introduce the topic of pediatric keratoconus, highlighting the importance of routine corneal topography and tomography in children and adolescents from predisposed groups. To attempt to ensure the early detection of keratoconus and its subclinical form, enabling early treatment, which brings better expected postoperative results.  Material and methods: Using the corneal tomograph Pentacam AXL we examined children and adolescents with astigmatism equal or greater than  2 diopters (in at least one eye) and patients with at least one risk factor such as eye rubbing in the case of allergic pathologies, positive family history of keratoconus or certain forms of retinal dystrophy. In total, we included 231 eyes (116 patients), of which 54 were girls and 62 were boys. RESULTS: The Belin-Ambrósio deviation index parameter was evaluated, in which we classified a total of 41 eyes as subclinical keratoconus and 12 eyes as clinical keratoconus. Next, the corneal maps were evaluated individually, in which we included a total of 15 eyes as subclinical keratoconus and 6 eyes as clinical keratoconus. In our group, compared to the control group, subclinical and clinical keratoconus occurred most often in the group of patients with astigmatism and in the group of so-called "eye rubbers". After individual evaluation, keratoconus occurred more frequently in boys than in girls in our cohort. CONCLUSION: Most patients with keratoconus are diagnosed when there is a deterioration of visual acuity and changes on the anterior surface of  the cornea. Corneal topography and tomography allows us to monitor the initial changes on the posterior surface of the cornea, and helps us to detect the subclinical form of keratoconus and the possibility of its early treatment. Therefore, it is important to determine which groups are at risk and groups in which corneal topography and tomography should be performed routinely.

LATE CHOROIDAL NEOVASCULAR COMPLICATIONS IN A PATIENT TREATED FOR RETINOBLASTOMA. A CASE REPORT.

AIM: Case report of choroidal neovascularization (CNV) detection in patient who was treated for bilateral retinoblastoma in early childhood. MATERIAL AND METHODS: Patient at 1.5 years of age treated for endophytic retinoblastoma stage 4 (according to the Reese-Ellsworth classification) bilaterally, with a positive mutation in the Rb1 gene. After undergoing bilateral retinal laser treatment and 6 cycles of systemic chemotherapy, the tumor remained inactive without other complications. At the age of 14, the boy developed visual impairment in his left eye with metamorphosis. Based on a local finding and other auxiliary examinations, he was diagnosed with CNV in the macular area at the interface of the tumor scar and the healthy retina of the left eye. RESULTS: After three applications of anti-VEGF (antibodies blocking vascular endothelial growth factor) substance intravitreally (bevacizumab 1.2 mg), there was a reduction in CNV and also an improvement in visual function.

A consonant construction of the hyaloid and retinal vascular systems by the angiogenic process.

There has been much debate as to whether the retinal vasculature forms by angiogenesis or vasculogenesis, thus angiogenesis is now accepted. We suppose that signals necessary for proper localization and development of the hyaloid and retinal vascular systems are already in place prior to the time at which these systems are developed. The remarkable conservation of vascular patterning suggests that specific genetic programs coordinate its formation. Evidence for a genetic program comes particularly from the characterization of gene-targeted mice and mutational analysis in zebrafish, but the exact genetic pathways remain poorly defined. Considering all the things from the aspect of angiogenesis significant differences exist between the mentioned vascular systems only in their lifetime (a) and location (b): (a) The hyaloid vasculature is a complex of transient intraocular vessels, while the retinal vessels are adapted for the whole life. (b) The hyaloid system fills the interior of the optic cup and this way "occupies" three-dimensional space while the distribution of the retinal vessels is relatively planar (two-dimensional) in the retina. We assume that retinal vessels are "built" in the same manner as the hyaloid vasculature and the outcomes at the embryological, histological, cellular and molecular levels confirm it. We show a consonant construction of both systems. The human organism does not have any rational reason to build up one system (i.e. the hyaloid vasculature) by angiogenesis and practically the same system (i.e. the retinal vessels) by another, de novo process, in the eye. It would be a waste of energy and various essential molecules. Thus, it seems that the retinal vascular system is an advanced copy of the hyaloid vessels (Tab. 1, Ref. 143).

Retinopathy of prematurity--epidemics, incidence, prevalence, blindness.

Currently, there are enough financial resources in industrial most developed countries to provide quality health care to the risk population of premature children. Neonatological units are equipped with state-of-the-art technological background, and highly qualified personnel are employed at the units. This as well allows providing optimum care of extremely immature newborns. ROP prevalence in these countries reaches approximately 5-8%. Today, a boom of surviving premature newborns can be seen in countries with medium-developed economy. Nevertheless, limited financing resources do not allow for standard high-level care. In such countries, the prevalence reaches up to 30%. In this respect, the "third ROP epidemic" is mentioned. Birth weight and gestational age parameters achieve significantly lower values in ROP-infants than in those not affected by the disease. Higher number of surviving immature newborns correlates with an increased risk of advanced ROP stages occurrence, while the frequency and degree of the disease are of inverse nature to the gestational age and birth weight (Tab. 1, Ref. 39).

Ocular manifestations of neurofibromatosis 1 - m. Recklinghausen.

Neurofibromatosis type 1 (NF 1) - morbus von Recklinghausen is an autosomal dominant phacomatosis with variable expression. The gene for NF 1 is located on chromosome 17q11.2. Incidence is 1 in 3500 live births. The diagnosis is made on the basis of clinical manifestations. Diagnosis requires the presence of 2 or more major criteria: 6 or more café au lait spots, 2 or more cutaneous neurofibromas or 1 plexiform neurofibroma, an optic nerve glioma, 2 or more iris Lisch nodules, axillary or inguinal freckling, bony lesions--pseudoarthrosis, sphenoid wing hypoplasia, or a first-degree relative with NF 1.

Ocular manifestations of neurofibromatosis 1--m. Recklinghausen.

Neurofibromatosis type 1 (NF 1)--morbus von Recklinghausen is an autosomal dominant phacomatosis with variable expression. The gene for NF 1 is located on chromosome 17q11.2. Incidence is 1 in 3500 live births. The diagnosis is made on the basis of clinical manifestations. Diagnosis requires the presence of 2 or more major criteria: 6 or more café au lait spots, 2 or more cutaneous neurofibromas or 1 plexiform neurofibroma, an optic nerve glioma, 2 or more iris Lisch nodules, axillary or inguinal freckling, bony lesions--pseudoarthrosis, sphenoid wing hypoplasia, or a first-degree relative with NF 1.

The problems of pediatric glaucoma.

The authors in the work define and introduce classification of the pediatric glaucomas and analyze the new opinions on the clinical and genetic aspects of this affection and their significance for ophthalmologic practice. Also they have dealt with recommended process in diagnostics. They analyse modern therapeutical problems of glaucoma in children. Authors have followed long-term the collection about 300 different pediatric glaucomas. Its purpose is by securing of reduction of intraocular pressure to preserve the satisfactory visual acuity and the visual field, eventually to reduce the progress of optic nerve damage. They introduce the brief survey about the newest pharmacological therapy in the conservative treatment of pediatric glaucoma and also they recommend the algorithm of surgical treatment, which is valid at this time and applied in their own praxis.

Marshall and stickler syndrome in one family.

The authors present the ocular finding in a patient sent to the Department of Paediatric Ophthalmology at the Children's University Hospital - Faculty of Medicine, Comenius University in Bratislava at the age of 3 months, with congenital glaucoma in her right eye and bilateral high myopia. The family anamnesis of the patient shows repeated occurrence of stunted growth, myopia, facial dysmorphia and cataract. The child's mother had high myopia, the mother's brother underwent cataract surgery, the child's grandmother and her sisters and the child's great grandmother had high myopia and glaucoma, and probably underwent cataract surgery at a young age. The child's mother and grandmother underwent a genetic examination, with a conclusion of Marshall syndrome. Within the framework of neonatal screening, poor cortical auditory evoked potential, a defect of the interventricular septum and bifid uvula were diagnosed in the child. With regard to the overall finding in the patient and the genetic family history, we suspected Marshall syndrome. A genetic examination determined Stickler syndrome type 1 with the presence of mutation in the COL2A gene (variant c.2710C >T (p.Arg904Cys,rs121912882)). Due to high intraocular pressure with the impossibility of compensation by medication, bilateral trabuculectomy was performed on the patient. At present the patient has intraocular pressure compensated with adjuvant medicamentous therapy. With regard to high myopia and pronounced degenerative changes on the periphery of the retina in the sense of lattice degeneration, preventive cryopexy of the retinal periphery is planned. A molecular genetic analysis helped diagnose the pathology as Stickler syndrome type 1, which manifested phenotype symptoms of Marshall syndrome or Stickler syndrome type 2. Key words: Marshall syndrome, Stickler syndrome, mid-facial dysmorfism, myopia, glaucoma, cataract.

Ophthalmological finding in a patient with lowe syndrome.

The authors present the ophthamological finding in a patient who at the age of 4.5 months was admitted due to a finding of total bilateral congenital cataract. The patient was observed by a neurologist for central hypotonia and mental retardation. Upon a complex examination of the patient, suspicion of Lowe syndrome was stated, which was confirmed by a metabolic examination and also by genetic tests. Upon an examination of the family, a genetic defect (mutation of OCRL1 gene) was confirmed also in the mother of the patient. A mild subcapsular opacification was present in the mother, beneath the posterior capsule. The patient was operated on for bilateral congenital cataract. Upon an examination under general anaesthesia, trabeculodysgenesis was diagnosed. Intraocular pressure remains within the norm. The patient is now aged 8 years, regularly monitored with regard to metabolic compensation, and by a neurologist and ophthalmologist, with satisfactory visual functions. Early diagnosis of the Lowe syndrome was determined on the basis of a complex examination of the patient within the framework of etiological diagnosis of bilateral congenital cataract. Key words: Lowe syndrome, oculo - cerebro - renal syndrome, congenital cataract, glaucoma, nystagmus.

[Treatment of Keratoconus with Corneal Cross-linking--Results and Complications in 2 Years Follow-up]. / Corneal cross-linking v liecbe keratokónusu--výsledky a komplikácie v dvojrocnom sledovaní.

OBJECTIVE: The objective of the study was to assessment of changes of monitored parameters after CXL. Incidence of complications were assessed in the whole group and in groups of patients divided according to the selected criteria. Evaluated parameters were also relations between them and in time. METHODS: The 86 eyes of patients with progressive keratoconus who underwent CXL according to the Dresden protocol in the years 2007-2009 at the Ophthalmic clinic FN Brno Bohunice were included in this study. RESULTS: There was observed significant increase of BCVA (letters--before CXL 42,30±10,35, 1st year after CXL (1Y) 44,68±10,04, p<0,01, 2nd year after CXL (2Y) 44,44±10,57, p<0,01) and SE (-5,95±3,98D, -5,27±3,84D, p<0,01, -4,94±3,68D, p<0,01), and decrease of maximum curvature of the cornea (MAX--before CXL 50,39±4,17D, 1Y 49,46±4,13D, p<0,01, 2Y 49,42±4,14D, p<0,01). Change of ultrasound CCT, polymegatisms, pleomorfisms and corneal endothelial cell density was not significant. The value of MAX is the most important parameter in estimating the effect of CXL. The highest incidence of corneal opacity after CXL was observed in the eyes of patients with III. stage of keratoconus over 40 years old, carrying hard contact lenses and with biomikroskopic symptom of keratoconus on the cornea. We found that corneal thickness measurement with Orbscan II and the mesurement of IOP with noncontact method is incorrect by patients after CXL. CONCLUSION: Corneal cross-linking of the cornea is safe and effective procedure of stopping the progression of keratoconus in 97% of eyes in the period up to 2 years after CXL.

[Risks in late diagnosis of retinoblastoma and their prevention]. / Riziká neskorej diagnostiky retinoblastómu a ich prevencia.

The study of the therapy of 57 patients with retinoblastoma and their 30-year follow-up a very significant problem of the delayed assessment of the diagnosis in this disease. The age of patients at the point of assessment of the diagnosis was delayed in average for 3 months after the appearance of first symptoms being especially leucocoria and strabismus, in hereditary Rb it yielded 10 months and in non-hereditary 36 months. The study emphasizes the risks of achieving lower therapeutic success rates and higher lethality in patients in very advanced stages of the disease. An improvement in parental care is assumed to represent a significant preventive measure against the late assessment of the diagnosis. The authors suggest an improvement in erudition of regional paediatrists together with fast provision of clinical care with the use of all diagnostic and therapeutic possibilities provided by modern medicine. (Fig. 4, Ref. 6.)

Posterior scleroplasty in children with severe myopia.

PURPOSE: To assess the influence of scleral reinforcement on the evolution of severe myopia in children. MATERIAL AND METHODS: Scleral reinforcement after Thompson was performed on 251 eyes of 154 children with high myopia from 2 to 18 years of age. The main indication criteria for surgery during the period 1992-2000 included: severe myopia more than -7 Diopters and the increase in refraction more than -1 D(per year. Zenoderm (porcin skin) was the main alloplastic material used during surgery. No serious complications were observed. The following main indicators of myopia advancement were investigated on a long-term basis and evaluated: axial length, refraction, visual acuity, fundus findings and perimetry. RESULTS: The positive influence of surgery on myopia advancement was observed in 100% of patients. In about 53% of operated eyes, myopia was absolutely stopped, and in about 47% of operated eyes, its advancement was considerably reduced. During 10 years of postsurgical check-up, stabilisation of myopia was achieved, the following in individual indicators: axial length--53.8% of eyes, refraction--52.9% of eyes, visual acuity--85% of eyes, fundus findings--58.6% of eyes, perimetry--59.1% of eyes. The advancement of myopia in other 47% of patients has been decreased from 1.1 D/per year before surgery to 0.1 D till 10 years after surgery. CONCLUSION: Scleral reinforcement is an effective and safe surgery that can stabilise the progression of severe myopia in children. (Tab. 6, Fig. 7, Ref. 12.).

[Ocular manifestations of toxocariasis]. / Ocné prejavy toxokarózy.

The paper reports about the ocular symptomatology of toxocariasis that represents a severe parasitic disease especially in children. Recently, the incidence of this disease is increasing. Diagnostic process has improved by means of newly developed laboratory methods. Ocular findings on retina are in toxocariasis identified very late. Despite many antihelmintics, steroids and surgical treatment, a poor treatment success has been achieved, and the sight remains often permanently severely affected. Because of the risk of blindness the most efficient arrangement is prophylaxy from the side of parents, teachers, veterinarions and the society as a whole. (Fig. 3, Ref. 6.)

[Ocular manifestation of toxoplasmosis in children]. / Ocné prejavy pri toxoplazmóze u detí.

The paper presents contemporary opinions on toxoplasmosis infection in the children, commonest form of posterior uveitis. Different clinical forms of ocular affection, current by available diagnostic methods, possible therapeutic approaches, their indications and contraindications, are analyzed. Risk of transplacentar infection and therapy of affected women are emphasized with the purpose of congenital toxoplasmosis prevention. (Fig. 2, Ref. 6.)

[Leber's hereditary optic neuropathy]. / Leberova hereditární neuropatie optiku (LHON).

BACKGROUND: Leber's hereditary neuropathy of the optic nerve (LHON) is manifested by bilateral affection of the eyes with acute or subacute loss of vision. The disease is caused by point mutations in the mitochondrial DNA (mtDNA) and is one of the most frequent mitochondrial diseases in the population. In patients with LHON 18 different point mutations in the mtDNA were described which correlate partly with the rate of progression of the disease and the severity and prognosis of the final affection of vision. METHODS AND RESULTS: The submitted paper deals with the results of molecular genetic examinations in three families with clinical manifestations of LHON. In three patients in the first family a homoplasmic mutation of mtDNA G3460A was found. In the second family in a young man with severely impaired vision a heteroplasmic mutation G3460A was found associated with a higher ratio of mutated mtDNA molecules than in his mother who is clinically healthy. In the third family the presence of homoplasmic mutation of mtDNA in position G11778A was detected. CONCLUSIONS: The diagnosis of LHON and genetic counselling in affected families should be based on close collaboration of ophthalmological and genetic departments with specialized laboratories engaged in molecular biological diagnosis of mitochondrial diseases.

[Foveal hypoplasia detection by optical coherence tomography]. / Detekcia foveálnej hypoplázie optickou koherentnou tomografiou.

PURPOSE: To evaluate the contribution of optical coherence tomography (OCT) in the diagnosis of foveal hypoplasia in children. MATERIAL AND METHODS: Children with foveal hypoplasia (FH) were examinated with device RTVue Fourier - domain (FD) - OCT, software - version 6.8 (Optovue Inc., Fremont, USA). A qualitative examination of the macular area was performed with single horizontal scan (1024 A-scans/frame). Macular thickness was measured and evaluated quantitatively with an automatic fast macular area protocol MM5 (Macular Map 5x5 mm). A control group of children was used for comparison. RESULTS: The quality was assessed with OCT image of the macula and quantitatively evaluated macular thickness and configuration in children with foveal hypoplasia. It was subsequently realized the comparison of macular OCT findings in healthy children. The OCT showed a reduction of foveal depression, continuous extension of the inner retinal layers through the area in which should be normally found fovea. Patients with foveal hypoplasia had thicker central macula and fovea than children in the control group. CONCLUSION: OCT in our group of patients confirmed the final diagnosis of foveal hypoplasia. FD-OCT is a noninvasive and quick method helpful in identifying retinal abnormalities in the diagnosis of foveal hypoplasia in children and may be useful in diagnosing patients with unexplained decrease in vision.