SUBCLINICAL OPTIC NEURITIS.

Acute optic neuritis is often associated with multiple sclerosis. It is considered to be the most common ocular symptom of multiple sclerosis. In addition to acute optic neuritis, in patients with multiple sclerosis, subclinical optic neuritis is also described. It is characterized by slow progression and bilateral involvement, thus being unnoticed by the patient. The purpose of the present study was to assess vision impairment in multiple sclerosis patients without a history of acute optic neuritis, using a number of functional tests including visual field testing by Octopus 101 perimetry N1 program, contrast sensitivity testing by Pelli Robson chart, and color vision by Ishihara pseudoisochromatic plates. The study included 35 multiple sclerosis patients aged 18-50 years, without subjective signs of vision impairment and visual acuity 1.0 according to Snellen. Visual field defects were found in 28 patients. The most common defects of visual fields were retinal sensitivity depression in peripheral zone and nerve fiber bundle defect. Reduced contrast sensitivity was found in 30 (86%) patients. Study results indicated multiple sclerosis patients free from signs of optic neuritis to suffer vision function impairment, as demonstrated by Octopus perimetry and contrast sensitivity testing with Pelli Robson charts.

THE ROLE OF FREQUENCY DOUBLING TECHNOLOGY PERIMETRY IN EARLY DETECTION OF DIABETIC RETINOPATHY.

The aim was to assess whether standard automated perimetry (SAP) and frequency doubling technology (FDT) perimetry are able to detect the effect of diabetes mellitus (DM) on retinal function in DM patients in the early stage of disease and to analyze which method is more specific and sensitive. A randomized cross-sectional study was conducted in three different groups of patients to compare the capability of these two methods to examine visual field and to detect the change in light sensitivity. Visual function was assessed in 60 adults with normal retinal finding, 60 adults with DM without clinically detectable retinopathy and 60 adults with DM and non-proliferative diabetic retinopathy but normal visual acuity. FDT perimetry and SAP were performed in all study patients. The presence and severity of diabetic retinopathy was determined by taking and evaluating two 50° field color photographs per eye, macula-centered and disc-centered. The following results were obtained by analyzing parameters in the groups of diabetic patients: sensitivity and specificity of SAP and FDT for medium sensitivity 86.7/33.3 (p<0.061) and 71.7/41.7 (p<0.228), respectively; for medium deficit 41.7/76.7 (p<0.063) and 65/50 (p<0.362), respectively; for loss of variance/pattern standard deviation (LV/PSD) 51.7/61.7 (p<0.536) and 61.7/51.7 (p<0.666), respectively; and for foveal sensitivity 81.7/36.7 (p<0.096) and 23.3/86.7 (p<0.839), respectively. Analysis of parameters between diabetics and control group yielded sensitivity and specificity for medium sensitivity 71.7/61.7 (p<0.001) and 70.8/55 (p<0.002), respectively; for medium deficit 56.7/60 (p<0.058) and 77.5/43.3 (p<0.037), respectively; for LV/PSD 58.3/58.3 (p<0.042) and 33.3/83.3 (p<0.437), respectively; and for foveal sensitivity 82.5/53.3 (p<0.001) and 28.3/85 (p<0.195), respectively. We concluded that neither of these methods was sensitive and specific enough to distinguish diabetics without retinopathy from diabetics with retinopathy. Both of these methods were highly specific and sensitive to distinguish diabetics from healthy subjects, but neither of these methods proved superior.

Visual impairment in children with cerebral palsy: Croatian population-based study for birth years 2003-2008.

AIM: To evaluate visual impairment (VI) in children with cerebral palsy (CP). METHODS: This population-based study included 419 children from the Surveillance of Cerebral Palsy in Europe (SCPE) C28 RCP-HR - Register of Cerebral Palsy of Croatia born 2003-2008. Vision in children with CP (according to SCPE) was classified as normal or impaired, with the subcategory of severe VI. The proportion of children with VI was assessed in groups with different CP type/subtype, gross and fine motor function, and gestational age (GA). RESULTS: A total of 266 children had some degree of VI (266/400; 66.5%), 134 had normal vision, and data on VI were unknown for 19 children. Severe VI was present in 44 children (44/400; 11%). The proportion of children with VI and severe VI increased with the Gross Motor Function Classification System and Bimanual Fine Motor Function levels. Children with bilateral spastic CP had the highest frequency of severe VI (14.9%). The percentage of severe VI in children with bilateral spastic CP was 53.8% in the group born <28 weeks of GA, 13.3% in the group born 28-31 weeks of GA, 11.1% in the group born 32-36 weeks of GA, and 24.4% in the group born >36 weeks of GA (λ2=4.95; df=6; P<0.001). CONCLUSION: Children with CP have a high prevalence of VI and severe VI, which is increasing with the level of motor impairment. Severe VI is significantly more common in children with bilateral spastic CP, especially among extremely premature infants.

DO ORTHOPTIC EXERCISES HAVE ANY INFLUENCE ON CHILDREN AND ADOLESCENTS DIAGNOSED WITH CONVERGENCE INSUFFICIENCY AND ATTENTION DEFICIT/HYPERACTIVITY DISORDER?

The aim was to determine whether improvement of near point of convergence (NPC) and binocular vision after orthoptic exercises had any impact on children and adolescents diagnosed with attention deficit/hyperactivity disorder (ADHD) and convergence insufficiency (CI). In this clinical trial, 50 children and adolescents aged 6 to 18 years diagnosed with ADHD and CI received orthoptic therapy that included home-based exercises (pencil push-ups and stereograms) and office-based therapy on synoptophore. Binocular vision and NPC were measured before, during and after therapy. Study subjects showed significant improvement (p<0.05) in NPC and binocular vision after orthoptic exercises. We found statistically significant correlation between stereovision improvement (Lang I) and near point of convergence, suggesting that improvement of binocular function is possible in children with ADHD and CI. Our results showed that NPC enhancement improved stereovision in patients with ADHD. Since progress of binocular function has positive effect on near work and diminishes visual symptoms in children and adolescents with ADHD and CI, it might be reasonable to suppose that orthoptic therapy helps these children improve concentration as well. Further studies are needed to determine whether it might have positive impact on attention.

EFFECT OF SUN EXPOSURE DURATION ON CYCLOOXYGENASE-2 EXPRESSION IN THE CONJUNCTIVA.

Pterygium is a multifactorial proliferative pathologic change of bulbar conjunctiva. The purpose of this study was to determine the effect of the duration of exposure to solar radiation (expressed in years) on the incidence of positive cyclooxygenase-2 (COX-2) finding in conjunctival tissue in two groups of patients. Group 1 consisted of 68 patients with primary pterygium having undergone conjunctival autograft transplantation. Group 2 consisted of 43 patients with morphologically unchanged conjunctivae that were harvested during cataract surgery. All 111 specimens were submitted to immunohistochemical staining for monoclonal COX-2 antibody (1:100; M361701 MO A-HU, Dako, Santa Clara, California, USA). The immunostaining intensity in the surface epithelium was scored using the following grading system: 0 no immunostaining; + weak immunostaining (few cells being positive focally or scattered); ++ medium immunostaining; and +++ strong immunostaining (diffuse staining throughout the tissue). The analysis of COX-2 activity yielded 29 (42.6%) positive findings in group 1 and 27 (62.8%) positive findings in group 2. Group 2 consisted of statistically significantly older individuals with a history of considerably longer sun exposure. Statistical analysis proved the duration of exposure to solar radiation to be the most important factor in positive COX-2 findings.

Levels of selected oxidative stress markers in the vitreous and serum of diabetic retinopathy patients.

PURPOSE: In diabetes, an impaired antioxidant defense system contributes to the development of diabetic retinopathy. The main objective of this paper was to find correlations of oxidative stress parameters within and between the vitreous and serum in patients with type 2 diabetes who had developed proliferative diabetic retinopathy. METHODS: The study included and compared two groups of patients who underwent vitrectomy: 37 patients with type 2 diabetes and proliferative retinopathy (PDR), and 50 patients with non-diabetic eye disorders (NDED). Vascular endothelial growth factor (VEGF), advanced oxidized protein product (AOPP), and oxidative stress markers (direct lipid hydroperoxidation (LPO), malondialdehyde (MDA), total superoxide dismutase (SOD), and glutathione (GSH)) were measured in the vitreous and serum of both groups and correlated with one another, between humoral compartments and with gender, age, and serum glucose levels. RESULTS: In the vitreous of PDR patients, VEGF, LPO, and MDA (p<0.05) were increased and SOD values were slightly lowered (p<0.05) than in NDED patients. Vitreous AOPP and GSH showed no differences between the groups. In the serum, AOPP, MDA, and SOD were increased (p<0.05) and VEGF was slightly increased (p<0.05) in the PDR group compared to NDED. With regard to gender, similar changes were recorded for both groups, except for the lower serum MDA in males than females in the NDED group. Advanced age showed no significant effect on changes of measured parameters in the vitreous. In the serum, VEGF was positively correlated (p<0.05) and MDA and SOD negatively correlated (p<0.05) with increasing age. Among measured parameters within and between the vitreous and serum, several correlative links occurred in the PDR group that were not present in the NDED group. The most prominent correlation changes were between serum LPO and vitreal LPO, serum SOD and vitreal LPO, serum LPO and serum SOD, and vitreal VEGF and serum SOD. CONCLUSIONS: Among the selected oxidative stress markers, SOD and LPO were highly correlative in both the vitreous and serum in PDR compared to patients without metabolic disorders. Their correlations suggested that monitoring their mutual alterations might be informative during PDR development and should be considered in further research.

Oxidative stress impact on growth hormone secretion in the eye.

AIM: To evaluate the influence of oxidative stress on extrapituitary growth hormone (GH) secretion in the eye and to analyze the interdependence between eye and serum GH levels under normal and hypoxic conditions. METHODS: Pars plana vitrectomy (PPV) was performed in 32 patients with developed proliferative diabetic retinopathy (PDR) and 49 non-diabetic controls, both of whom required this procedure as part of their regular treatment in the period from April 2013 to December 2014. During PPV, vitreous samples were taken and blood was simultaneously collected from the cubital vein. GH levels in serum and vitreous samples were measured by electrochemical luminescence assay. Oxidative stress was measured by enzyme-linked immunosorbent assay of advanced oxidation protein products (AOPP) and lipid hydroperoxide (LPO) in serum and vitreous. RESULTS: Serum AOPP levels were significantly higher than vitreous levels in both groups (P<0.001 for each group) and LPO levels were significantly higher only in PDR group (P<0.001). There was a significant positive correlation between serum and vitreous LPO levels in PDR group (r=0.909; P<0.001). Serum GH levels were significantly higher than vitreous levels in both groups (P<0.001 for each group). Serum GH levels were significantly higher in PDR group than in controls (P=0.012). Vitreous GH values were slightly higher in PDR group, but the difference was not significant. CONCLUSION: Our study confirms that GH production in the eye is autonomous and independent of oxidative stress or pituitary GH influence.

Corticosteroid therapy in patients with non-arteritic anterior ischemic optic neuropathy.

Non-arteritic anterior ischemic optic neuropathy is one of the most common conditions affecting the optic nerve in the elderly. It may lead to severe visual loss. Typical symptoms are painless impairment of visual function accompanied by relative afferent pupillary defect, edema of the optic disc and visual field defects. Aim is to present 38 patients with nonarteritic anterior ischemic optic neuropathy who were treated with corticosteroid therapy. This prospective study involved 38 patients, 20 men and 18 women aged 60-75 years who were treated with corticosteroid therapy. The study included patients with visual acuity in the affected eye from 0.1 to 0.8 according to Snellen. Every patient underwent clinical examination, the Octopus 900 perimetry in G program, laboratory testing, while the compressive optic neuropathy was rule out with MSCT of the brain and orbits. The most common forms of visual field defect are altitudinal defect and diffuse depression. Corticosteroid therapy led to recovery in 65% of patient, in 30% of patients did not change, while the deterioration occurred in 5% of patients.

Contact lenses as the best conservative treatment of newly diagnosed keratoconus--epidemiological retrospective study.

Keratoconus is a progressive, non-inflammatory corneal ectasia characterized by thinning and weakening of the corneal stroma which results in its' protrusion. The onset is during puberty and progresses until the fourth decade of life. In earlier stages, good visual acuity can be provided with spectacles. With progression, contact lenses are considered to be a better therapy. Aim of this study was to determine if there is statistically significant difference between best corrected visual acuity (BCVA) obtained by spectacles and contact lenses in newly diagnosed keratoconus patients, as well as to determine which type of contact lenses provide better BCVA in keratoconus patients. We conducted a 5-year retrospective study of all 2891 patients attending our Contact Lens Department for the first time, searching for patients newly diagnosed with keratoconus. Data were obtained on gender, age, education level, treated eyes, corneal changes, keratoconus severity, BCVA with spectacles, contact lenses and best fitted contact lens type. All patients underwent standard ophthalmic exam, refractometry and keratometry have been done, followed by a spectacles correction and lens fitting. Wilcoxon signed rank test was used for statistical analysis. Results showed that of all 2891 patients examined for the first time, 137 patients (4.74%) have been newly diagnosed with heratoconus, there was male bias (72.26%), mean age 27.7 +/- 9.9 years. Most patients had high school education (51.11%), 3.70% had present corneal changes, 50.37% had mild heratoconus. Majority had keratoconus on both eyes (36.3%) or keratoconus of right eye (26.67%). There was a statistically significant difference (p<0.001) between the BCVA obtained with contact lenses (0.82 +/- 0.21 Snellen chart) rather than spectacles (0.37 +/- 0.27 Snellen chart). The best corrected visual acuity was achieved with rigid gas permeable (RGP) lenses in majority of kera- toconus eyes (51.85%), with semi-gas permeable (SGP) lenses in 43.39%, in 4.23% with polymethyl methacrylate (PMMA) lenses and with hard-soft gas permeable (GP) contact lenses in 0.53% of keratoconus eyes. We have showed that there is a statistically significant difference in BCVA achieved better with contact lenses than with spectacles. RGP lenses are most frequently used in conservative treatment of heratoconus, but SGP lenses were also shown to be a good option that gives equally satisfying final visual acuity with subjective comfortable feeling of contact lens wear.

Effect of the against the rule myopic astigmatism on the near vision of the elderly.

In the two groups of patients with myopic astigmatism the uncorrected near vision was tested after catatract surgery. Each group with 20 patients ages 60-80. All patients enrolled in study have uncorrected far vision 0.5 or better on Snellen tables. In the first group patients were with the rule after surgery myopic astigmatism (1-1.50 Diopter), and in the second group were patients with against the rule after surgery myopic astigmatism (1-1.50 Diopter). Patients in the second group with against the rule astigmatism achieved significantly (p<0.01) better uncorrected near vision.

Automated static perimetry: the influence of myopic anisometropia on evaluation of visual field.

The aim of study was to establish which level of myopic refractive error influences visual field defects in automated static perimetry, if these defects are typical, and if optimal correction normalized the visual field. The study included 100 patients (200 eyes) divided into three groups according to the severity of the myopic refractive error: group A (till -3.25 Dsph), group B (-3.50 Dsph to -5.25 Dsph) and group C (-5.50 Dsph to -8.00 Dsph). The control group included 20 emmetropes (40 eyes). This study confirms that optimal corrected and uncorrected myopia up to -3.25 Dsph does not produce quantitative visual field defects, when tested by static automated perimetry. Even in optimally corrected myopics, with myopia higher than -5.50 Dsph, visual field defects on gray scale can be found. Defects are in the intermediary zone with more prominent defects in the upper quadrants. Visual field indices (MD, MS, LV RF) were completely normalized.

The role of optical coherence tomography (OCT) in optic neuritis (ON).

Axonal and neuronal degeneration are important features of multiple sclerosis (MS) and other neurologic disorders that affect the anterior visual pathway. Optical coherence tomography (OCT) is a non-invasive technique that allows imaging of the retinal layers. Our aim was to examine retinal nerve fiber layer (RNFL) thickness and macular volume (MV), measred by OCT in patients with history of optic neuritis (ON). Patients with chronic ON had significantly decreased mean RNFL thickness and total MV when compared to acute ON eyes, controls and unaffected fellow eyes. There was also statistically significant difference between two chronic groups, with lower values in group with history of acute ON. OCT provides us unique insight in structural changes in the anterior visual pathway, therefore it may complement our existing diagnostic tests and, as a potential outcome measure, help develop more effective therapeutic strategies for ON and MS patients.

Role of NMO-IgG in distinguishing the type of optic neuritis.

PURPOSE: To emphasize the importance of neuromyelitis optica (NMO)-immunoglobulin G (IgG) antibodies testing in patients with typical optic neuritis (ON) refractory to steroid treatment. METHODS: Two patients were evaluated with ON refractory to steroid therapy and poor visual acuity; they were tested for NMO-IgG antibodies. RESULTS: Brain magnetic resonance imaging was normal in both patients. The serum and cerebrospinal fluid were positive for NMO-IgG antibodies. Magnetic resonance imaging of the cervical and thoracic spine revealed lesions longer than three vertebral segments and the diagnosis of NMO was confirmed. Treatment with plasma exchange and immunosuppressive therapy resulted in marked improvement of visual acuity. This improvement was sustained. CONCLUSIONS: The testing for NMO-IgG antibodies is important for distinguishing ON in NMO from multiple sclerosis in cases of ON refractory to steroid treatment. These cases suggest that testing for NMO-IgG antibodies should be performed in comparative trials on a larger series.

The role of the spectral domain ocular coherence tomography in detection of age-related macular degeneration.

Age-related macular degeneration (ARMD) is one of the most common causes of the vision loss and blindness in developed countries. Among other harmful effects, exposure to the UV radiation is the most prominent factor for the development of the disorder. Using the method of SD OCT (Spectral Domain Ocular Coherence Tomography) we performed measurement of the neurosensory retinal thickness of 19 eyes of low vision patients from the population of Primorsko-Goranska County of Republic of Croatia, with dry form of the terminal macular degeneration. These results we compared with control measurements performed on 28 eyes of healthy, normal vision subjects from same County. We determined following parameters: central foveal thickness (CFT), macular volume (MV) and mean foveal thickness (MFT) in the both groups. Results showed statistically significant reduction of CFT in the group of normal vision female patients when compared to males, while any significant difference of CFT between total groups of normal vision individuals and low vision patients was not detected. Furthermore, we noticed statistically significant (p < 0.000001) decrease of the MV in the group of the low vision patients in comparison to healthy subjects and statistically significant (p < 0.000001) reduction of the MFT of the low vision patients when compared to normal vision individuals. In our study we detected the absence of any significant difference of the CFT between healthy and low vision population, what looks like controversial finding, because neurosensory retina in the ARMD is thin and atrophic, but on the other side it is known that fixation point in low vision patients is translocated from the damaged fovea to extrafoveal region, usually above the fovea, where neurosensory retina is of the normal thickness, but with the less sensitivity. Furthermore, our results suggest possible connection of higher incidence of ARMD with lower CFT in females. Owing to the thicker neurosensory retina in males and better protection, damaging effect of the UV irradiation, which is the proven factor of ARMD development, is smaller. From the evolutionary point of view it is possible that males in all vertebrates have more resistant macula because during the evolutionary process they have spent much more time outside in the sunlight than females.

Enlarged Foveal Avascular Zone after Whiplash Injury-Acquired Berlin's Edema.

We describe a case of optical coherence tomography angiography (OCTA) changes in the foveal avascular zone (FAZ) in a patient that had suffered Berlin's edema after a whiplash neck injury. The patient reported central scotoma throughout the 1-year follow-up, confirmed by visual field examination. OCTA showed FAZ enlargement of the left eye as compared to the healthy right eye in the superficial capillary layer and even more in the deep capillary layer. To the best of our knowledge, FAZ enlargement has not been previously described by OCTA after whiplash-related macular injury.

Prostatic carcinoma metastatic to the optic nerve.

Optic nerve can be infiltrated with various tumors and inflammatory processes, with a considerable prevalence of primary over secondary tumors. Metastases of gastric carcinoma to the optic nerve are less frequently, and those of prostatic carcinoma very infrequently observed. A 66-year-old man presented with metastasis to the optic nerve with consequential vision loss to the level of light perception developed two years after prostatic surgery. Systemic therapy with methylprednisolone resulted in a satisfactory vision function recovery. According to literature data, prostatic carcinoma metastases to the optic nerve occur very rarely. In our patient with the optic nerve infiltration found on the first clinical examination, papillary edema was associated with the signs of optic nerve functional impairment (visual acuity, visual field, unilateral RAPD). An infiltrative process involving a distal portion of the optic nerve usually does not cause papillary alterations, and produces a clinical picture of retrobulbar optic neuropathy, such as that observed in our patient on the second clinical examination, showing the signs of optic nerve damage.

[The role of patient compliance in the management of glaucoma]. / Uloga suradnje bolesnika u lijecenju glaukoma.

AIM: The aim of the study was to evaluate patient cooperation in glaucoma treatment. METHODS: We evaluated data collected by an anonymous questionnare from 98 glaucoma patients who answered 6 questions regarding their compliance and persistence in glaucoma treatment. RESULTS: Study results revealed 50% of patients to fail taking their antiglaucoma therapy regularly. Patients on monotherapy showed better compliance and higher level of satisfaction with treatment than those on combination antiglaucoma therapy consisting of 2 or 3 eyedrops. Discontinuation of persistence was recorded in 31% of patients, whereas 51% of patients did not present for control visits every six months as suggested by their ophthalmologist. CONCLUSION: Patients are more compliant and persistent with antiglaucoma monotherapy than with combined therapy. Greater compliance and persistence with ocular hypotensive therapy may improve the outcomes in glaucoma.

Coexistence of ochronosis and B 27 positive ankylosing spondylitis.

We describe a 49-year-old man with coexistence of ochronosis and B27 positive ankylosing spondylitis. This is the first report documenting the simultaneous occurrence of ochronosis and B27 positive ankylosing spondylitis, with no positive familiar history for seronegative spondylarthropathies. The relations of these rheumatic diseases are discussed.

Minor head trauma and isolated unilateral internuclear ophthalmoplegia.

Internuclear ophthalmoplegia is a syndrome that develops due to a lesion of the medial longitudinal fasciculus. This lesion is mostly caused by multiple sclerosis (usually bilaterally), and only rarely by head injury. A case is presented of unilateral internuclear ophthalmoplegia as an isolated sequel of minor head trauma, which eventually resolved. A 40-year-old woman with isolated internuclear ophthalmoplegia secondary to closed head trauma with anatomical lesions of the mesencephalon in the region of medial longitudinal fasciculus is described. A minor contusion was detected by magnetic resonance imaging. Diplopia resolved in 5 months. In conclusion, internuclear ophthalmoplegia should be considered in the differential diagnosis in patients with recent head injuries showing adduction impairment. The connection between the clinical picture and anatomical lesions is visualized by magnetic resonance imaging.

Leber's hereditary optic neuroretinopathy (LHON) associated with mitochondrial DNA point mutation G11778A in two Croatian families.

Leber's hereditary optic neuroretinopathy (LHON) is manifested as a bilateral acute or subacute loss of central vision due to optic atrophy. It is linked to point mutations of mitochondrial DNA, which is inherited maternally. The most common mitochondrial DNA point mutations associated with LHON are G3460A, G11778A and T14484C. These mutations are linked with the defects of subunits of the complex I (NADH-dehydrogenase-ubiquinone reductase) in mitochondria. The G11778A mitochondrial DNA point mutation is manifested by a severe visual impairment. In this paper two Croatian families with the LHON G11778A mutation are presented. Three LHON patients from two families were younger males which had the visual acuity of 0.1 or below, the ophthalmoscopy revealed telangiectatic microangiopathy and papilloedema, while Goldmann kinetic perimetry showed a central scotoma. The mothers and female relatives were LHON mutants without symptoms, whereas their sons suffered from a severe visual impairment. Molecular diagnosis helps to explain the cause of LHON disease.