Mitochondrial genome variation in male LHON patients with the m.11778G > A mutation.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder with symptoms limited to a single tissue, optic nerve, resulting in vision loss. In the majority of cases it is caused by one of three point mutations in mitochondrial DNA (mtDNA) but their presence is not sufficient for disease development, since ~50% of men and ~10% women who carry them are affected. Thus additional modifying factors must exist. In this study, we use next generation sequencing to investigate the role of whole mtDNA variation in male Polish patients with LHON and m.11778G > A, the most frequent LHON mutation. We present a possible association between mtDNA haplogroup K and variants in its background, a combination of m.3480A > G, m.9055G > A, m.11299 T > C and m.14167C > T, and LHON mutation. These variants may have a negative effect on m.11778G > A increasing its penetrance and the risk of LHON in the Polish population. Surprisingly, we did not observe associations previously reported for m.11778G > A and LHON in European populations, particularly for haplogroup J as a risk factor, implying that mtDNA variation is much more complex. Our results indicate possible contribution of novel combination of mtDNA genetic factors to the LHON phenotype.

Immunomodulation on the ocular surface: a review.

The increasing understanding of immune mechanisms changed our perception of the ocular surface, which is now considered a compartment of the common mucosal immune system. It offered the possibility to alter the physiological immune response on the ocular surface and effectively combat inflammation, which impairs stability of the tear film and causes tear hyperosmolarity, causing symptoms of dry eye disease. The paper provides an overview of ocular surface anatomy and physiology, explains the underlying mechanisms of dry eye disease and discusses novel and promising treatment modalities, such as cyclosporine A, biological therapies using autologous serum and various growth factors as well as experimental treatment methods which are currently being investigated.

Is it appropriate to perform anterior segment reconstruction in amblyopic eye following penetrating trauma in childhood?

We present a case of diagnostic and surgical management in an amblyopic eye following penetrating trauma in childhood. The 75-year-old female patient experienced the trauma at the age of 4. The eye was amblyopic, but after thorough investigations (ultrasonography, ultrabiomicroscopy, visual evoked potentials) the eye underwent anterior segment reconstruction. Visual evoked potentials allowed us to assess optic nerve function, while ultrabiomicroscopy allowed us to plan the surgical procedure. Although we observed quite a small visual acuity improvement, the subjective improvement reported by the patient was fairly significant (NEI VFQ-25 questionnaire). The cosmetic effect of the black pupil was also important.

Next-generation sequencing of ABCA4: High frequency of complex alleles and novel mutations in patients with retinal dystrophies from Central Europe.

Variation in the ABCA4 locus has emerged as the most prevalent cause of monogenic retinal diseases. The study aimed to discover causative ABCA4 mutations in a large but not previously investigated cohort with ABCA4-related diseases originating from Central Europe and to refine the genetic relevance of all identified variants based on population evidence. Comprehensive clinical studies were performed to identify patients with Stargardt disease (STGD, n = 76) and cone-rod dystrophy (CRD, n = 16). Next-generation sequencing targeting ABCA4 was applied for a widespread screening of the gene. The results were analyzed in the context of exome data from a corresponding population (n = 594) and other large genomic databases. Our data disprove the pathogenic status of p.V552I and provide more evidence against a causal role of four further ABCA4 variants as drivers of the phenotype under a recessive paradigm. The study identifies 12 novel potentially pathogenic mutations (four of them recurrent) and a novel complex allele p.[(R152*; V2050L)]. In one third (31/92) of our cohort we detected the p.[(L541P; A1038V)] complex allele, which represents an unusually high level of genetic homogeneity for ABCA4-related diseases. Causative ABCA4 mutations account for 79% of STGD and 31% of CRD cases. A combination of p.[(L541P; A1038V)] and/or a truncating ABCA4 mutation always resulted in an early disease onset. Identification of ABCA4 retinopathies provides a specific molecular diagnosis and justifies a prompt introduction of simple precautions that may slow disease progression. The comprehensive, population-specific study expands our knowledge on the genetic landscape of retinal diseases.

[Molecular aspects of corneal neovascularization]. / Neowaskularyzacja rogówki w ujeciu molekularnym.

In this article, we try to describe the fundamentals of the molecular mechanisms implicated in the corneal neovascularization. Corneal avascularity is maintained by a subtle balance between the constant and active production of proangiogenic and angiostatic factors. At present, the prospect of clinical and therapeutic application of this knowledge seems to be distant, but some of the recent studies investigating the already known substances instill optimism. This work is based on data from the recently published reports on the corneal angiogenesis in its complexity.

[Evaluation of effectiveness and tolerance of treatment with azithromycin 1.5% eye drops in bacterial conjunctivitis]. / Ocena skutecznosci i tolerancji 1,5% kropli ocznych azytromycyny w leczeniu bakteryjnego zapalenia spojówek.

INTRODUCTION: Azithromycin is a macrolide class antibiotic, recently adapted for topical use in ophthalmology. It is effective against the most frequent pathogens found in bacterial conjunctivitis, Gram positive and Gram negative bacteria. Azithromycin has the specificity to have sustained high tissue levels: after repeated instillation, it has been shown to reach sustained concentrations above the MICs of susceptible bacteria for 4 days in tears and for 7 days in conjunctiva. THE AIM OF STUDY: To investigate the effectiveness and tolerance of treatment with Azithromycin 1.5% eye drops in bacterial conjunctivitis. MATERIALS AND METHODS: The prospective study included 40 patients (69 eyes) with purulent bacterial conjunctivitis; aged 21-70 years; average: 38.05 Patients were treated with 1.5% azithromycin eye drops topically twice-daily for 3 days. Conjunctival swabbings were taken at the 1st and the 7th +/- 1 day of the treatment. Effectiveness and tolerance of eye drops were assessed in 7th +/- 1 day from the beginning of the treatment. RESULTS: Bacteriological cultures were positive before treatment in 34 eyes (49.28%), negative--35 eyes (50.72%). In 69 eyes with bacterial conjunctivitis the following microorganisms were identyfied (34 eyes): Streptococcus pneumoniae 23.53% (8 eyes), Staphyllococcus aureus 23.53% (8 eyes), Staphyllococcus epidermidis 20.59% (7 eyes), Haemophilus influenzae 17.65% (6 eyes), Morganella Morgani 2.94% (1 eye), Proteus mirabilis 2.94% (1 eye), Enterococcus species 2.94% (1 eye), Streptococcus viridians 2.94% (1 eye), Moraxella (Branhamella) catarrhalis 2.94% (1 eye). Positive bacteriological culture at the 7th day of treatment--2 eyes (1 eye--Staphyllococcus epidermidis MSCNS, 1 eye--Morganella Morgani). Clinical recovery or significant improvement were observed in 68 of 69 evaluated eyes. CONCLUSIONS: Three-day topical therapy with azithromycin 1.5% eye drops is an effective and well tolerated therapy for purulent bacterial conjunctivitis.

A family with 3460G>A and 11778G>A mutations and haplogroup analysis of Polish Leber hereditary optic neuropathy patients.

Three mutations in mitochondrial DNA complex I genes are responsible for over 90% of Leber hereditary optic neuropathy (LHON) cases in Europe. A family with two LHON mutations--practically homoplasmic 11778G>A and varying levels of 3460G>A--was found during analysis of Polish patients. DNA and visual acuity was analyzed in four affected brothers and their unaffected sister and mother as well as in their step brother. Four male patients experienced vision loss around the age of 20 while for their step brother the onset was late--at the age of 33. No additional neurological symptoms were observed and both women were completely asymptomatic. The mutation occurred in a haplogroup H background, the most common one in both the Polish population and among patients. Double LHON mutations are extremely rare, and this particular combination has not been previously described in the literature.

Therapeutic use of a lotrafilcon A silicone hydrogel soft contact lens as a bandage after LASEK surgery.

PURPOSE: Soft contact lenses may be used as a bandage after corneal refractive surgery. Silicone hydrogel contact lenses offer the advantage of increased oxygen permeability over conventional hydrogel lenses for this application. To evaluate a silicone hydrogel contact lens as a continuous wear bandage applied after laser-assisted sub-epithelial keratomileusis (LASEK). METHODS: We conducted a prospective, open-label, non-randomized clinical trial involving thirty patients treated with unilateral LASEK. Patients were fitted with a lotrafilcon A (Focus NIGHT & DAY; CIBA Vision, Duluth, GA) silicone hydrogel soft contact lens that was worn continuously for 3 to 4 days post-operatively. Lens movement and slitlamp evaluations of conjunctival hyperemia 1, 2, and 3 days after surgery (DAS) were recorded, as was the condition of the corneal epithelium after lens removal. Subjective comfort was rated by the patients along with the presence of symptoms or pain. RESULTS: Post-blink lens movement was evaluated by investigators as "very good" or "good" in 87% of eyes at 1 DAS, in 73% at 2 DAS, and in 60% at 3 DAS. Conjunctival hyperemia was assessed as normal or trace in 96% of eyes at 1 DAS, in 76% at 2 DAS, and in 67% at 3 DAS. An average of 80% of eyes showed normal or trace conjunctival hyperemia during the trial. The condition of the corneal epithelium after contact lens removal was rated as "very good" in 13% or "good" in 73% of eyes. An average of 77% of subjects reported "very good" or "good" comfort during the trial. Symptoms or pain were rated as "absent" or "mild" by all subjects at 1 DAS and 2 DAS and by 96% at 3 DAS. An average of 99% rated symptoms or pain as either "absent" or "mild" during the trial. CONCLUSIONS: The lotrafilcon A lens was found to be an effective and well-tolerated bandage lens after LASEK.

Therapeutic use of a silicone hydrogel contact lens in selected clinical cases.

PURPOSE: To evaluate a silicone hydrogel contact lens as a continuous-wear bandage in selected clinical cases, a prospective, open, nonrandomized clinical study was conducted. METHODS: Seventy eyes from 70 patients with anterior segment conditions for which therapeutic lenses were indicated were enrolled in the study. In most patients (47 eyes, 67%), the presenting condition was bullous keratopathy. Patients were fitted with a lotrafilcon A silicone hydrogel lens (Focus Night & Day) that was worn continuously for 7 to 30 days, and the concomitant therapies were used. The corneal condition was assessed, and subjective comfort was recorded for 7 days to 18 months after fitting (mean follow-up, 69 days). RESULTS: Of 70 eyes, 64 (91%) showed improvement in the clinical condition of the eye, and 66 (94%) rated comfort when wearing the lens as very good or good. CONCLUSIONS: The study lens was found to be an effective and well-tolerated bandage lens in these selected patients.