Neurofibromatosis type I and unilateral ophthalmic artery occlusion

Etiological investigation of a 15-year-old boy with left ophthalmic artery occlusion led us to a diagnosis of neurofibromatosis type I as there were numerous large cafe-au-lait spots, axillary freckling, and brain MRI changes consistent with a hamartoma. In light of the present case, ophthalmic artery occlusion may be a rare feature of neurofibromatosis type I besides more commonly described cerebrovascular changes.     

Negative ERGs in mucopolysaccharidoses (MPS) Hurler–Scheie (I-H/S) and Hurler (I-H)-syndromes

The configuration and progression of the ERG in two children with mucopolysaccharidosis (MPS) I H/S (Hurler-Scheie syndrome) and MPS I H (Hurler syndrome) is described. Physical examination, biochemical analysis, ophthalmic examination and electroretinography were performed. The Hurler-Scheie patient (case 1) showed negative scotopic but normal photopic ERGs, which remained unchanged over 2 years. The Hurler patient (case 2) showed negative scotopic and photopic ERGs which did not alter after bone marrow transplantation (BMT). One year after BMT, further b-wave amplitude reduction had caused the ERGs to become more negative. The electronegative configuration of the ERGs suggests that, in these cases of MPS, the primary retinal abnormality in MPS I may be faulty synaptic transmission from photoreceptors to more proximal elements, deficient bipolar responsivity, or Muller cell disease. Further degradation with time suggests the defect to be progressive with BMT causing little or no improvement. In the Hurler-Scheie syndrome case, the defect appears to spare the cone system and to show little or no progression.     

Ocular histopathology of systemic mucopolysaccharidosis, type II-A (Hunter syndrome, severe)

A case of mucopolysaccharidosis, Type II-A (Hunter syndrome, severe) is described, with emphasis on ocular ultrastructural findings. Single membrane-bound structures containing fibrillogranular and, less commonly, multi-membranous material were found in conjunctival epithelium, pericytes and fibrocytes; corneal epithelium, keratocytes, and endothelium; trabecular endothelium; iris pigmented epithelium, smooth muscle, and fibrocytes; ciliary pigmented and nonpigmented epithelium and fibrocytes; retinal pigment epithelium and ganglion cells; optic nerve astrocytes and pericytes; and sclerocytes. The most striking accumulation was in the nonpigmented ciliary epithelium. These findings are compared with those seen in MPS II-B, and in other systemic mucopolysaccharidoses. The nature and distribution of inclusions are not specific to any one disorder, but help to signal the presence of one of the storage disorders. Distension of corneal keratocytes may play a role in the corneal clouding seen in some of these disorders. The importance of tissue examination, especially conjunctival biopsy, in the diagnosis of storage disorders and in assessment of future modes of therapy for the mucopolysaccharidoses is discussed.     

Multimodal image analysis of the retina in Hunter syndrome (mucopolysaccharidosis type II): Case report

Introduction: We report a case of retinal and posterior ocular findings in a 33-year-old man diagnosed with Hunter syndrome (Mucopolysaccharidosis type II) in a multimodal imaging way.

Case presentation: Our patient was complaining of blurred night vision for the past 3 years. He had not received any systemic treatment for Hunter syndrome. Vision acuity was 20/20 in both eyes and corneas were clear. Fundus examination revealed bilateral crowded and hyperemic optic nerve heads (elevated in the ocular ultrasound) and areas of subretinal hypopigmentation. There was hyperautofluorescence at the central fovea and perifovea, and a diffuse bilateral choroidal fluorescence in angiography. Macular SD-OCT showed a thinning of the external retina at the perifovea in both eyes. Visual field testing showed a bilateral ring scotoma. The full field ERG was subnormal, with a negative response in the scotopic phase. Visual Evoked Potencial test and cranial MRI were normal.

Conclusion: Our multimodal analysis reported here attempted to contribute to the knowledge of the natural history of GAG deposition in the eye, focusing on the retina and retinal pigment epithelium. Defining this natural history is essential for a proper comparison with Hunter patients receiving systemic treatment, thus determining if it can or cannot improve retinal function in humans with this disorder.     

Cytochrome P4501B1 mutations cause only part of primary congenital glaucoma in Ecuador

Purpose: To determine the role of cytochrome P4501B1 ( CYP1B1 ) mutations in causing primary congenital glaucoma (PCG) in a cohort of Native Americans from Quito, Ecuador. Materials and methods: Seventeen patients with PCG from 15 Native American families were recruited from the Ophthalmology Clinic at Hospital Metropolitano, Quito, Ecuador. Experienced ophthalmologists examined all affected study subjects. Purified DNA was prepared from peripheral blood samples and CYP1B1 coding exons (exons 2 and 3) were amplified and sequenced. Southern blot was performed only on those affected patients who showed no mutations in the CYP1B1 coding exons. Results: The molecular basis of PCG in two families was determined: two novel mutations (a deletion and a point mutation) and one novel polymorphism in CYP1B1 were identified in addition to a previously described single amino acid substitution. Southern blot analyses on whole genomic DNA from affected individuals in whom no mutations were identified by the direct PCR/sequencing approach did not detect any large rearrangements or mutations outside the coding region. Conclusion: These findings suggest that mutations in CYP1B1 are not a major cause of PCG in this population and that at least one additional locus for this condition is responsible for most cases. Further, the PCG phenotype did not correlate readily with the molecular basis of the disorder, suggesting that careful clinical analysis of the phenotype cannot predict the molecular basis of the disease with accuracy.     

Ocular and electrophysiological findings in a patient with Sly syndrome

Background: Sly syndrome (Mucopolysaccharidosis Type VII) is an autosomal recessive metabolic storage disorder due to mutations in the GUSB gene encoding the enzyme beta-glucuronidase. Deficiency of this lysosomal enzyme impairs the body’s ability to break down the glycosaminoglycans – dermatan, heparan and chondroitin sulphate. Coarse facial features and macrocephaly are typically seen along with bony and skeletal abnormalities, including joint contractures and short stature. Widespread involvement occurs in many other tissues including cardiopulmonary, gastrointestinal, and neurological systems. In view of the rarity of Sly syndrome the ophthalmic features have not been well described.Materials and methods: Case report of a 16-year-old boy with Sly syndrome with serial OCT, ocular ultrasound, and electroretinogram (ERG).Results: Corneal clouding was present but there was no evidence of glaucoma or optic neuropathy. Despite no clinical evidence of retinopathy, electrophysiology showed reduced photopic and scotopic responses, particularly involving the b-wave which appears progressive. OCT showed normal foveal architecture and normal retinal nerve fiber thickness.Conclusion: Corneal clouding was noted in this patient and there is no evidence of glaucoma or optic neuropathy. Although retinopathy has not been previously described in Sly syndrome, the ERG changes in this patient suggest that retinopathy may be a feature of MPS VII.     

Clinical and genetic studies of an autosomal dominant cone-rod dystrophy with features of Stargardt disease

Much progress has been made in the past five years in the understanding of Leber congenital amaurosis (LCA) and allied early-onset retinal dystrophies, various forms of stationary sensory retinal blindness, and genes that are involved in the development of the retina. Uncomplicated Leber congenital amaurosis has been associated with mutations of six genes: GUCY2D (encoding RetGC-1) at 17p13.1, RPE65 at 1q31, CRX at 19q13.3, AIPLI at 17p13.1, CRB1 at 1q31-3, and RPGRIP at 14q11. A similar early-onset severe retinal degeneration phenotype has been associated with mutation of TULP1 at 6p21.3. Leber appreciated that the condition he described merged with the phenotypes of early childhood-onset severe retinal degenerations. This insight has been confirmed at the molecular level for mutations of GUCY2D , RPE65 , CRX , AIPL1 , and CRB1 , which cause not only LCA, but also early-childhood and even adult-onset retinal degenerations. This paper reviews the new finding of LCA from mutations of CRB1 and discusses the molecular basis of X-linked blue monochromacy, autosomal recessive congenital achromatopsia from mutations of the genes for ACHM2 ( CNGA3 ) and ACHM3 ( CNGB3 ), X-linked congenital stationary night blindness (CSNB) from mutations of CACNA1F (incomplete CSNB) and NYX (complete CSNB), and the enhanced S-cone syndrome from mutation of the developmental gene, NR2E3 at 15q23, which appears to regulate the development of M- and L-cones from S-cones. These discoveries have opened new areas of cellular and developmental biology for future research into the causes of retinal blindness.     

Corneal hysteresis in mucopolysaccharidosis I and VI

Purpose: High intraocular pressure (IOP) and glaucoma are often suspected in patients with mucopolysaccharidosis (MPS). To determine corneal hysteresis (CH) and IOP in children with mucopolysaccharidosis I‐Hurler (MPS I‐H) and MPS VI. Methods: Clinical measurements with ocular response analyzer (ORA). Results: In seven patients, five with MPS I‐H treated with stem cell transplantation (SCT), and two with MPS VI, one treated with SCT and the other with enzyme therapy, the IOP was examined with ORA. Ocular response analyzer measurements were made at a median age of 8.7 years in the patients with MPS I‐H and at a median age of 9.3 years in the patients with MPS VI. Earlier measurements had raised suspicion of high IOP in one patient. The ORA showed an increased CH and a falsely high IOP values in all 14 eyes. The recalculated IOPs were normal in all 14 eyes. Mild to severe corneal opacities were present in all 14 eyes. Optic disc areas, borders and cupping were clinically normal in the 12 of 14 eyes that were possible to examine. Severe corneal opacities hampered optic disc evaluation in the older patient with MPS VI. Three eyes in two patients had normal thickness of the retinal nerve fibre layer measured with scanning laser polarimetry with corneal compensation (GDx VCC). No patient was diagnosed or treated for glaucoma. Conclusion: The IOPs are often falsely high because of an increased resistance of the cornea and correlate to the extent of corneal clouding. In this small, cross‐sectional study, it appears that corneal resistance is directly correlated with corneal clouding, although a longitudinal study that evaluates resistance as the cornea clears with treatment would provide more direct evidence that corneal deposits are directly related to resistance. A correct measured IOP can avoid unnecessary medical or surgical hypotensive treatment.     

Cannabinoids and the eye

Cannabis ranks among the most commonly used psychotropic drugs worldwide. In the context of the global movement toward more widespread legalisation, there is a growing need toward developing a better understanding of the physiological and pathological effects. We provide an overview of the current evidence on the effects of cannabinoids on the eye. Of the identified cannabinoids, Δ⁹-tetrahydrocannabinol is recognized to be the primary psychotropic compound, and cannabidiol is the predominant nonpsychoactive ingredient. Despite demonstrating ocular hypotensive and neuroprotective activity, the use of cannabinoids as a treatment for glaucoma is limited by a large number of potential systemic and ophthalmic side effects. Anterior segment effects of cannabinoids are complex, with preliminary evidence showing decreased corneal endothelial density in chronic cannabinoid users. Experiments in rodents, however, have shown potential promise for the treatment of ocular surface injury via antinociceptive and antiinflammatory effects. Electroretinography studies demonstrating adverse effects on photoreceptor, bipolar, and ganglion cell function suggest links between cannabis and neuroretinal dysfunction. Neuro-ophthalmic associations include ocular motility deficits and decrements in smooth pursuit and saccadic eye movements, although potential therapeutic effects for congenital and acquired nystagmus have been observed.     

Reflexes and the eye

Reflexes are an essential part of protective and homeostatic function, both in general terms and with specific reference to ocular structures. A wide range of stimuli and responses, with varying degrees of central processing, is involved in such reflexes. The simplest reflexes are monosynaptic, such as the stretch or myotatic reflex. More complex polysynaptic reflexes are involved in many regulatory and protective functions - these include autonomic as well as somatic reflexes. Ocular autonomic reflexes include the oculocardiac, pupillary, accommodative and lacrimatory reflexes. Ocular somatic reflexes include eyelid and extra-ocular muscle reflexes (such as Bell's phenomenon, vestibulo-ocular and optokinetic reflexes). An account of the above reflexes is given in the format of an essay, modified from the FRACO Part I Examination in Physiology. The topic was ‘Discuss reflex activities with particular reference to the eye’. The content is based on several of the texts recommended for the Part I Examination, as listed under references.     

Cytomegalovirus and the eye

Following primary infection, cytomegalovirus (CMV) establishes latent infection in myeloid progenitor cells and intermittent viral reactivation from activated macrophages or dendritic cells, which is brought under control by strong virus-specific CD4+ T-cell and CD8+ T-cell responses. CMV retinitis characterized by spreading retinal necrosis due to viral cytopathic effect occurs in patients who have impaired T-cell function as a result of transplantation, AIDS, or immuno-suppressive treatment. The diagnosis of CMV retinitis can be confirmed by PCR amplification of viral DNA in aqueous. When administered intravenously, the antiviral drugs Ganciclovir and Foscarnet have modest penetration into the vitreous compared with direct intra-vitreal injection. In randomized trials of HIV-associated CMV retinitis, a Ganciclovir implant was consistently superior to intravenous Ganciclovir in preventing progression of retinitis. CMV is also implicated in two forms of anterior segment disease in immuno-competent adults, namely CMV anterior uveitis and CMV corneal endotheliitis.     

Caffeine and the eye

Caffeine, a popular psychostimulant that acts as an adenosine receptor antagonist, is the most widely used drug in history, consumed daily by people worldwide. Knowledge of the physiological and pathological effects of caffeine is crucial in improving public health because of its widespread use. We provide a summary of the current evidence on the effect of caffeine on the eye. Most of the research conducted to date is in relation to cataract and glaucoma, two of the most common eye diseases among the elderly.     

Objectively measuring anterior segment alterations in the eyes of mucopolysaccharidoses: Its utility in early diagnosis of glaucoma

Purpose:Our study aimed to evaluate the utility of the anterior segment morphometry for objectively assessing anterior segment architectural changes of corneal clouding in the mucopolysaccharidoses (MPS) cohort and to investigate whether these measurements correlate with the slit-lamp findings on the cornea and early diagnosis of glaucoma.Methods:This retrospective study involved 70 eyes of 35 children with cloudy cornea due to MPS variants. Anterior segment architectural alterations were measured using anterior segment imaging and biometry in MPS children and compared with controls.Results:Mean age of the cohort at the time of assessment was 7.9 ± 4.5 years. Males constituted two-thirds of the cohort. Variants of MPS with cloudy cornea were as follows: Type I (62%), Type IV (11%), and Type VI (22%). Morphometric measurements were available in 22 eyes of 11 MPS children and an age-matched healthy control group. There were significant differences between MPS cohort and controls in refraction in Diopters (5.03 ± 0.39 and 0.01 ± 0.04; P < 0.0001), axial length (AXL) in mm (21.39 ± 0.28 and 23.04 ± 0.28; P = 0.0002), average keratometry in Diopters (40.67 ± 0.44 and 42.83 ± 0.44; P < 0.0001), anterior chamber depth (ACD) in mm (2.92 ± 0.07 and 3.65 ± 0.07; P < 0.0001), and intraocular pressure (IOP) in mmHg (25.2 ± 2.0 and 14.1 ± 2.3; P = 0.0003). Secondary glaucoma was observed in 28% of the MPS cohort.Conclusion:The anterior segment morphometry in the cloudy cornea due to MPS provides an objective measurement of anterior segment architectural changes, thus diagnosing early-onset secondary glaucoma. These findings highlight that cloudy cornea due to MPS variants merits close monitoring throughout life.     

AIDS and the eye

The acquired immune deficiency syndrome (AIDS), is a recently described irreversible dysfunction of cell-mediated immunity in homosexuals, intravenous, drug abusers, and hemophiliacs, with subsequent development of potentially lethal opportunistic infections and/or unusual neoplasms, such as Kaposi's sarcoma. A prospective evaluation of ophthalmic findings in 14 patients with AIDS revealed that 8 patients had ophthalmoscopically and biomicroscopically significant ocular abnormalities, including peripapillary cotton-wool spots of changing frequency and diameter, retinal hemorrhages, progressive cytomegaly virus (CMV) retinitis, acute destructive retinal necrosis, periphlebitis, CMV conjunctivitis and keratitis, and in one patient a conjunctival Kaposi's sarcoma. All patients with AIDS and abnormal ocular findings carry a poor prognosis. Early detection of ocular manifestations is important, since most patients with AIDS are visually asymptomatic, and the ophthalmic presentation may be the primary one, and the initiating contact leading to diagnosis and permitting the prognosis to be assessed.