Spasm of the near reflex:a common diagnostic dilemma?

AIM:To report the clinical characteristics and diagnostic procedures used in patients with spasm of the near reflex(SNR),in order to present common investigation strategies and diagnostic pitfalls.METHODS:Retrospective case series of twenty-two patients,mainly children,with SNR or accommodation spasm(AS).AS was diagnosed on the basis of blurred vision and a difference of>2 dioptres between manifest and cycloplegic retinoscopy.If esotropia and miosis were present,the patients were diagnosed with SNR.All patients underwent visual acuity testing,orthoptic evaluation,assessment of refraction before and after cycloplegia,and dilated fundoscopy.Additional diagnostic investigations,such as neuroimaging,lumbar puncture(LP),electrophysiology and blood tests,were also recorded.Screen use among children was assessed in hours per day.RESULTS:There were 19 female and 3 male patients(age range 7-33 y,median=10 y).Seventeen patients had AS and 5 patients had SNR,with episodic blurry vision and headaches being the most common symptoms.Brain neuroimaging was performed in six patients(27%),although only one had a history of brain trauma.Two of those patients underwent visual evoked potentials and three also underwent LP and received intravenous steroid therapy.The majority of patients(90%)reported prolonged daily screen time(>2 h/d),and in 55%of cases there were concurrent social problems or psychological triggers.Treatment consisted of careful explanation of the condition,atropine1%eye drops and full cycloplegic correction by means of bifocal glasses.CONCLUSION:The diagnosis of SNR and AS may be challenging,because symptoms are usually intermittent and nonspecific,and a large number of patients are often subjected to redundant and potentially time-consuming examinations and treatment,that may exaggerate the underlying psychological disorder.Hence,detailed clinical testing and assessment of psychosocial profile is necessary,in order to avoid unnecessary investigations.Neuroimaging should be performed only in selected cases.Finally,due to prolonged screen use SNR and AS may become more frequent in the future.     

First Identification of a Triple Corneal Dystrophy Association: Keratoconus,Epithelial Basement Membrane Corneal Dystrophy and Fuchs’ Endothelial Corneal Dystrophy

Purpose

To report the observation of a triple corneal dystrophy association consisting of keratoconus (KC), epithelial basement membrane corneal dystrophy (EBMCD) and Fuchs’ endothelial corneal dystrophy (FECD).

Methods

A 55-year-old male patient was referred to our cornea service for blurred vision and recurrent foreign body sensation. He reported bilateral recurrent corneal erosions with diurnal visual fluctuations. He underwent corneal biomicroscopy, Scheimpflug tomography, in vivo HRT confocal laser scanning microscopy and genetic testing for TGFBI and ZEB1 mutations using direct DNA sequencing.

Results

Biomicroscopic examination revealed the presence of subepithelial central and paracentral corneal opacities. The endothelium showed a bilateral flecked appearance, and the posterior corneal curvature suggested a possible concomitant ectatic disorder. Corneal tomography confirmed the presence of a stage II KC in both eyes. In vivo confocal laser scanning microscopy revealed a concomitant bilateral EBMCD with hyperreflective deposits in basal epithelial cells, subbasal Bowman''s layer microfolds and ridges with truncated subbasal nerves as pseudodendritic elements. Stromal analysis revealed honeycomb edematous areas, and the endothelium showed a strawberry surface configuration typical of FECD. The genetic analysis resulted negative for TGFBI mutations and positive for a heterozygous mutation in exon 7 of the gene ZEB1.

Conclusion

This is the first case reported in the literature in which KC, EBMCD and FECD are present in the same patient and associated with ZEB1 gene mutation. The triple association was previously established by means of morphological analysis of the cornea using corneal Scheimpflug tomography and in vivo HRT II confocal laser scanning microscopy.Key words: Keratoconus, Fuchs’ endothelial corneal dystrophy, Epithelial basement membrane dystrophy, Cogan dystrophy, Confocal microscopy, ZEB1     

The taming of the shrew? The immunology of corneal transplantation

Corneal transplantation, first reported a century ago, is the oldest and most frequent form of solid tissue transplantation. Although keratoplasty is also considered as the most successful transplant procedure, several studies indicate that the long term survival of corneal grafts is even lower than that of transplanted parenchymatous organs. Despite the immune privilege enjoyed by the cornea and anterior segment of the eye, immunologic graft rejection is a major limitation to corneal transplantation. This review gives an update on corneal immunobiology and the mechanisms of corneal graft rejection, focusing on antigen presentation, as well as on the molecular and cellular mediators of this particular immune response.     

The value of “en toto” globe submission in the assessment of high-risk retinoblastoma cases and staging

Purpose

To evaluate the importance of “en toto” globe submission in the assessment of high-risk pathological findings in retinoblastoma cases, aiming at identifying the additional value from full globe examination of enucleated eyes (including the calottes).

Methods

Retrospective histopathological case series of eighty-one enucleated globes with the clinical diagnosis of retinoblastoma, histopathologically examined at King Khaled Eye Specialist Hospital (KKESH) between January 2010 and December 2013. We included retinoblastoma eyes with any type of invasion (more than pT1) in which the globe was submitted “en toto.” All cases were histopathologically classified according to the American Joint Cancer Classification (AJCC TNM classification, 2009 6th edition).

Results

81 enucleated globes were examined, out of which 30 globes were classified as high-risk cases (more than pT1). 8 cases had massive choroidal invasion in both the PO sections and calottes. 5 cases had focal choroidal invasion in both. One case has massive choroidal invasion in calottes with very superficial ON head invasion. Two cases were found to have focal choroidal invasion in the calottes with prelaminar ON invasion. In these three cases (10%), the presence of focal or massive choroidal invasion in the calottes has affected the classification.

Conclusions

This study consolidates the guidelines recommended in the consensus meeting: from the International Retinoblastoma Staging Working Group on the pathology guidelines for the examination and evaluation of prognostic risk factors in retinoblastoma eyes. Full globe submission and examination should be the routine accepted practice universally even in underdeveloped countries.

     

Analysis of COL8A2 Gene Mutation in Japanese Patients with Fuchs’ Endothelial Dystrophy and Posterior Polymorphous Dystrophy

Purpose To determine whether Japanese patients with Fuchs endothelial corneal dystrophy (FECD) and posterior polymorphous dystrophy (PPMD) carry mutations in the COL8A2 gene, and to investigate the possible pathogenicity of the COL8A2 gene in these corneal dystrophies.Methods DNA analysis of the COL8A2 gene was performed in 15 unrelated Japanese patients with FECD, and 5 patients with PPMD using polymerase chain reaction and direct sequencing. Mutation screenings were also performed in 36 unrelated normal volunteers as controls, as well as slit-lamp and specular microscopy.Results Two types of heterozygous missense mutations of the COL8A2 gene (R155Q and T502M) in 5 of 15 FECD probands (R155Q, 3/30 chromosomes, 10.0%; T502M, 3/30 chromosomes, 10.0%) were found. No mutation was detected in the coding region of the COL8A2 gene in the remaining 10 patients with FECD nor in any of the 5 patients with PPMD. These two mutations were also found in normal Japanese volunteers (R155Q, 5/72 chromosomes, 6.9%; T502M, 11/70 chromosomes, 15.7%). The chromosomal frequency of the two mutations was not significant between the patients and normal controls.Conclusions The R155Q and T502M mutations of COL8A2 may not be the causative defect in the Japanese FECD and PPMD patients examined in this study. Jpn J Ophthalmol 2004;48:195–198 © Japanese Ophthalmological Society 2004     

No evidence for a genetic blueprint: The case of the “complex” mammalian photoreceptor

Despite the intensity of the search for genes causing inherited retinal degenerations over the past 3 decades, of the approximately 200 disease genes identified to date, all appear to be ordinary housekeeping genes specifying proteins playing basic structural and functional roles in the mature photoreceptor cells. No genes or genetic elements have been identified which can be construed as having a specific morphogenic role, directing the development of the cytoarchitecture of any particular retinal cell. The evidence suggests that the cytoarchitecture of the retinal photoreceptors, although enormously complex, arises from the self-organization of the cells constituents without any regulation or direction from an external genetic blueprint.     

Malignant transformation of optic disc melanocytoma? A clinical dilemma at presentation with a review of the literature

Malignant transformation of optic disc melanocytoma is an uncommon feature, although in the past a few cases have been reported. Though our case, a healthy 30-year-old female, presented with all clinical features of melanocytoma, the triad of moderate visual loss, elevation of the lesion of 5.2 mm and an atypical ultrasonic picture could be an indication of malignant change at presentation. In the event of a moderate visual loss, long-term follow-up with serial fundus photographs and ultrasonic measurements is necessary for further management.     

Review of the treatment of Graves’ ophthalmopathy: The role of the new radiation techniques

Graves ophthalmopathy (GO) is an autoimmune disorder and the most frequent extrathyroidal manifestation of Graves’ disease. GO is an inflammatory process leading to an increased volume of the extraocular muscles and orbital connective and adipose tissues associated with multiple histopathological changes. Despite recent progress in the understanding of its pathogenesis, GO often remains a major diagnostic and therapeutic challenge. It has become increasingly important to classify patients into categories based on disease severity and activity. Low doses of radiotherapy (RT) have demonstrated a benefit in the treatment of moderate-to-severe GO with very few side effects. New RT techniques deliver a more conformal dose distribution to the target and decrease the dose to normal healthy tissue minimizing the risk of side effects. In this review we briefly analyzed the pathogenesis of GO and discussed the most relevant therapeutic approaches, with particular emphasis in the new RT technics. Appropriately designed and powered clinical studies are necessary to determine the most effective treatment with the lowest risk of side effects.     

The effect of β-blocker on ERG c-wave of the rabbit

The toxicity of -blocker, Befunolol HCl (BFE), to the retinal pigment epithelium was investigated electrophysiologically. Rabbit in vivo ERG b- and c-waves were recorded after intravitreal injections of 0.1 ml of 0.25, 1, 2, 4, 6 and 10% BFE solutions with osmolalities of 304, 340, 383, 432, 493 and 618 mOsm repsectively. Phosphate solutions with osmotic pressure corresponding to the BFE solutions were injected as control.In eyes injected with 0.25% BFE, amplitude of either b- and c-waves were unchanged for 60 min, while in eyes injected with BFE with a higher concentration than 1%, the b-waves attenuated but the c-waves enhanced in proportion to the BFE concentrations.In the control group, the b-waves attenuated and the c-waves enhanced by the injection of the high osmotic phosphate solutions up to 500 mOsm, which corresponded to the osmotic pressure of 6% BFE, but attenuated by the phosphate solutions higher than 600 mOsm.Based on the above result, no acute toxicity of BFE to the retina was suggested in dose of its therapeutic use. The attenuation of b-waves by BFE was likely due to the influence of osmotic pressure since no significant difference in the b-waves amplitudes was found between BFE and equimolar phosphate solutions. However, high concentration of BFE itself was suggested to exhibit an effect to enhance the c-wave because a manifest difference was observed in the c-wave amplitudes between the group at higher BFE concentrations and the correspond control group.     

Review of the Series “Disease of the Year 2011: Toxoplasmosis” Pathophysiology of Toxoplasmosis

Toxoplasma gondii is a major cause of chronic parasitic infection in the world. This protozoan can cause retino-choroiditis in newborns and in adults, both immunocompetent and immunodeficient. This disease tends to be recurrent and can lead to severe visual impairment. The authors review current knowledge on the role of parasite genetics in influencing susceptibility to ocular toxoplasmosis and on the immuno-pathogenesis of this disease.     

The present status of the calibration of Schiøtz tonometers

Summary Stimulated by Friedenwald's studies a number of investigators has made new measurements of the principal factors involved in tonometer calibration, namely, the intraocular pressure during the application of a tonometer, the volume of the corneal indentation produced by the tonometer, and the coefficient of ocular rigidity. The new measurements are undoubtedly better than those upon which Friedenwald based his calibration scale of 1954 as well as its 1955 revision. The validity of the latter scale is, fortunately, not seriously threatened by the new measurements.These measurements also clearly demonstrate the highly problematic nature of any postmortem calibration technique. A closer approach to the actual pressure equivalents of the tonometric readings may be expected from calibration studies on human eyes in vivo and in situ.

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Zusammenfassung Angeregt durch die Arbeiten von Friedenwald haben sich während der letzten drei Jahre eine Reihe von Autoren mit Messungen des Druckes während der Belastung des Auges mit dem Tonometer (P_t), des Volumens der Hornhauteindellung durch das Tonometer (V_c) und des Rigiditätskoeffizienten des Auges befasst. Die neuen Messungen sind zweifellos genauer als die älteren Messungen, weiche Friedenwald zur Berechnung seiner Eichkurven vom Jahre 1954 und der revidierten Eichkurven vom Jahre 1955 verwendete. Trotzdem werden die Eichkurven vom Jahre 1955 durch die neuen Messungen nicht ernstlich in Zweifel gestellt.Die neuen Messungen zeigen mit grosser Deutlichkeit wie problematisch Eichversuche am toten Auge sind. Die wirklichen Druckequivalente der tonometrischen Messungen könnten wahrscheinlich mit grösserer Genauigkeit durch Eichversuche am lebenden menschlichen Auge bestimmt werden.

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Résumé Stimulés par les études de Friedenwald, plusieurs auteurs ont mesuré au cours de ces dernières années la tension intraoculaire durant la pesée du tonomètre (P_t), le volume de la dépression cornéenne due à l'instrument (V_c) et le coefficient de rigidité de l'oeil. Il est certain que les nouvelles mensurations sont meilleures que celles qui ont fourni à Friedenwald la base pour son échelle de calibration de 1954 et pour celle révisée de 1955. Toutefois, la validité de cette dernière n'en est pas sérieusement menacée.Les nouvelles mesures démontrent également que tout essai de calibration partant de l'oeil de cadavre n'a qu'une valeur très relative. Il est probable que les études faites sur l'oeil humain vivant nous donneraient les équivalents des mesures tonométriques avec une précision nettement plus grande.

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University of Illinois, College of Medicine, Chicago.