Mario R. Pannarale

Comparison of Apraclonidine and Timolol in Chronic Open-angle Glaucoma: A Three-month Study

PURPOSE To compare the safety and efficacy of apraclonidine ophthalmic solution 0.25% and 0.5% (both given 3 times daily) to timolol maleate (0.5%) given twice daily, in primary open-angle glaucoma or ocular hypertension. METHODS This study was a 90-day prospective, multicenter, double-masked, randomized, parallel group trial. Intraocular pressure (IOP) measurements were made between 8:00 and 10:00 AM before the morning dose (i.e., up to 12 hours after the evening dose of glaucoma medication) and at 4:00 PM (i.e., 8 hours after the morning dose of glaucoma medication). Patients with off-therapy IOP of greater than 22 mmHg and less than 35 mmHg were entered into the study and were assessed 14, 30, and 90 days after treatment. RESULTS Sixty-nine patients were enrolled; there were no significant demographic differences among the three study groups. All three treatments significantly reduced IOP over 90 days (P < 0.011). For apraclonidine 0.5%, IOP reductions from 25.8 +/- 3.2 mmHg (pretreatment) to 20.4 +/- 4.00 mmHg (day 90) were observed; for apraclonidine 0.25%, from 25.7 +/- 3.05 mmHg (pretreatment) to 22.1 +/- 4.24 mmHg (day 90); and for timolol 0.5% from 26.1 +/- 3.79 mmHg to 21.1 +/- 5.91 mmHg (day 90). The 90-day period of therapy was completed by 12 patients treated with apraclonidine 0.5%, 21 patients treated with apraclonidine 0.25%, and 23 patients treated with timolol 0.5%. There were no serious adverse events. Fourteen of 22 patients (0.5% apraclonidine) and 21 of 23 patients (0.25% apraclonidine) tolerated the drug well; ocular allergy developed in the remaining patients treated with apraclonidine, which resolved upon discontinuation. CONCLUSIONS Apraclonidine effectively lowers IOP associated with open-angle glaucoma or ocular hypertension; these pilot results will need to be confirmed by a larger pivotal study. Long-term therapy for some patients may be inhibited by ocular allergy for which there was a higher incidence to the 0.5% apraclonidine solution than to the 0.25% solution in this study. Apraclonidine may be of value as an additional therapy for open-angle glaucoma in selected patients.

Plasma endothelin-1 concentrations in patients with retinal vein occlusions.

AIMS To investigate whether plasma levels of endothelin-1 (ET-1), a potent vasoconstricting peptide that is crucial in regulating retinal blood flow, were elevated in patients with retinal vein occlusion (RVO). METHODS ET-1 plasma concentrations were determined by radioimmunoassays in a double blind fashion in a group of 18 selected patients with RVO, in 20 healthy age matched non-smoking, normoglycaemic, normotensive control subjects, and in 15 patients with uncomplicated essential hypertension in the same age range. RESULTS Patients with RVO had significantly increased ET-1 plasma levels (14.22 (SD 4.6) pg/ml) compared with both normal subjects (7.90 (1.6) pg/ml; p < 0.05) and hypertensive patients (8.50 (2.9) pg/ml; p <0.05). The highest concentrations of circulating ET-1 were found in patients with RVO of the ischaemic type (16.97 (3.5) pg/ml; p < 0.01; n = 7). Systemic hypertension alone did not account for the observed increase in plasma ET-1 concentrations. CONCLUSIONS These findings raise the possibility that the increased circulating ET-1 levels in patients with RVO may be a marker of the occlusive event, thereby suggesting that ET-1 homeostasis may be relevant to RVO pathogenesis and retinal ischaemic manifestations.

Autosomal dominant simple microphthalmos.

Congenital bilateral microphthalmos is a rare malformation of the eye, which ranges from extreme to mild reduction of total axial length. Microphthalmos may occur as an isolated ocular abnormality or as part of a systemic disorder, and different classifications of the condition have been attempted. We describe a large pedigree with 14 persons in four generations affected with bilateral microphthalmos without other ocular or systemic signs. An autosomal dominant trait with complete penetrance is proposed. Five subjects underwent a complete ophthalmological evaluation. The total axial length was measured by A scan ultrasonography in all persons. Ultrasonography showed a reduction of the total axial length (range 18.4-19.7 mm) and a reduced vitreous cavity length (range 11.4-13.5 mm) in all investigated patients. All the patients had microcornea (range 8-9.7 mm). No other ocular anomalies or associated systemic malformations were found. A review of published reports also suggests that simple, partial, posterior, pure microphthalmos and nanophthalmos are similar clinical entities sharing total axial length and vitreous cavity length reduction. Therefore, the term simple microphthalmos is proposed to identify these clinical conditions.

Correlation between Goldmann perimetry and maximal electroretinogram response in retinitis pigmentosa

To evaluate the relationship between Goldmann perimetry and maximal electroretinographic responses in patients with retinitis pigmentosa, analyses were performed on 220 affected subjects and separately on two subgroups with autosomal dominant (n = 35) and autosomal recessive (n = 29) inheritance. Electroretinograms were recorded averaging 100 iterations elicited with a 20-lux/s, 0.5-Hz white flash ganzfeld stimulation. The peripheral isopters of the visual fields were delimited with I4e, IIIe and V4e targets, measured on conventional perimetry charts with a light pen and expressed in square centimeters. Unlike most previously published reports, this investigation showed a definite correlation (p = 0.0001) between maximal electroretinographic response amplitude and visual field areas. This correlation was more evident for I4e and IIIe isopters (r = 0.89 and 0.87, respectively) than for V4e isopter (r = 0.69). This phenomenon appears to be related to distortion occurring on standard isometric charts and to spatial summation effects in the peripheral field. Such correlations held for both the autosomal dominant and autosomal recessive subgroups. It appears that, if enough accuracy is provided, maximal electroretinographic responses and Goldmann visual fields are both good measures of the remaining functioning retina in nonsyndromic retinitis pigmentosa, irrespective of inheritance models and dystrophic patterns.

The ocular phenotype of the Bardet-Biedl syndrome Comparison to non-syndromic retinitis pigmentosa

PURPOSE To investigate 20 patients affected with Bardet-Biedl (BB) syndrome and compare them to an age-matched group of 70 non-syndromic patients with retinitis pigmentosa (RP) to identify hallmarks peculiar to the BB phenotype. METHODS Patients were examined clinically and with functional tests (color vision, kinetic perimetry, electroretinography, ocular motility tests). Fundus findings were numerically graded for statistical purposes. RESULTS Recurrent ocular features in BB patients were early and severe reduction of visual acuity, constantly altered color vision, high incidence of strabismus and nystagmus, mild-to-severe atrophic changes of the optic disc, and frequently absent or minimal pigmentary retinal changes. Visual acuity was more closely correlated to optic disc than to macular conditions. These findings were remarkably different from non-syndromic RP. CONCLUSIONS This investigation further suggests that retinopathy in BB syndrome has features distinctive from those in non-syndromic RP. The early occurrence of optic disc atrophy in the BB syndrome, even in those patients with healthy maculas, suggests that optic atrophy could often be primary in nature and might play a major role in decreasing central vision in BB patients. Variability of some findings is in line with the documented heterogeneity of the BB syndrome.

Autosomal-dominant Retinitis Pigrnentosa Associated with an Arg-135-Trp Point Mutation of the Rhodopsin Gene: Clinical Features and Longitudinal Observations

Purpose: To report the clinical and functional characteristics of patients affected with autosomal-dominant transmitted retinitis pigmentosa (adRP) from a large Italian pedigree in which a point mutation predicting the Arg-135-Trp change of rhodopsin was identified by polymerase chain reaction-single-strand conformation polymorphism analysis. Methods: Seven patients, ranging in age from 6 to 41 years, underwent a full clinical ophthalmologic evaluation, kinetic visual field testing, and electroretinographic testing. Results: In agreement with previous reports, this rhodopsin mutation yielded a particularly severe phenotype, both clinically and functionally. The evaluation of patients from this pedigree in the first and second decade of life demonstrated that retinal function is still electroretinographically measurable at least until 18 years of age, although reduced to 2% to 4% of normal. Longitudinal measures showed that the rate of progression of the disease was unusually high, with an average 50% loss per year of electroretinographic amplitude and visual field area with respect to baseline. Later in the course of the disease, macular function is also severely compromised, leaving only residual central vision by the fourth decade of life. Conclusions: The phenotype associated with mutations in codon 135 of the rhodopsin molecule appears to have an unusually high progression rate and yields an extremely poor prognosis. These distinctive features make the Arg-135-Trp phenotype substantially different from the general RP population, and also from many of the other adRP pedigrees with known rhodopsin mutations reported to date. Ophthalmology 1996,-103:1443-1452

Clinical heterogeneity of dominant optic atrophy: the contribution of visual function investigations to diagnosis

Abstract• Background: The variability of the visual function impairment in dominant optic atrophy (DOA) makes it difficult to diagnose the disease within genealogies. Physiologic investigations were conducted on a family with DOA to evaluate methods of detecting clinical and subclinical signs in obligate heterozygotes, in order to identify affected subjects within the genealogy and to formulate the individual and reproductive risks • Methods: Investigations included tests for color vision, contrast sensitivity function (CSF), kinetic and static computerized perimetry, transient pattern reversal visual evoked potentials (VEPs) and steady-state flash VEPs • Results: Eight subjects from the pedigree were diagnosed as having DOA. Two of them were unaware of their affection, and six showed wide clinical variability. CSF paralleled the central visual impairment, but was also slightly impaired in the two unaware subjects. Static computerized perimetry disclosed mild sensitivity defects in the central visual fields in these two patients. VEPs showed heteregeneous results as well, ranging from normal findings to severely altered tracings • Conclusions: This investigation suggests that combined clinical and functional evaluation is necessary to diagnose DOA. Particularly, the combined use of computerized perimetry, CSF, and VEPs allowed the identification of cases at a subclinical stage.

Clinical Features of Autosomal Dominant Retinitis Pigmentosa Associated with the GLY-188-ARG Mutation of the Rhodopsin Gene

Several different rhodopsin gene mutations have been identified in the last years in pedigrees with autosomal dominant retinitis pigmentosa (adRP). In view of the differences in the molecular nature and location of these mutations, defining the phenotype has become increasingly important in order to identify the clinical counterpart to the different functional abnormalities of the photopigment molecule.1–9

Scotopic Threshold Responses and Rod Intensity-Response Functions as Sensitive Indicators of the Carrier Status In X-Linked Recessive Retinitis Pigmentosa

In previous studies several authors described modifications of ERG responses in X-linked recessive retinitis pigmentosa (xLRP) carriers (1–8). Investigations on the intensity-response functions of the rod ERG also demonstrated reduction of Vmax in subjects with ophthalmoscopic evidence of the carrier status (pigmentary changes and/or tapetal-like reflex) (4). In patients affected with RP abnormalities of the Oscillatory Potentials (OPs) have also been demonstrated (9,10), suggesting a coexisting impairment of the inner retinal layers. Abnormalities of rod sensitivity were also found at the psychophysical level to flickering stimuli (11).

Validity of Scleral Surgery for the Treatment of Vitreo-Retinal Tractions and Proliferations

Scleral indentation techniques can be used not only to close retinal breaks but also to reduce vitreo-retinal tractions and retractions. To a certain extent proper applications of scleral indentations can sometimes avoid or at least restrict the use of vitreous surgery.