© Borgis - Postępy Nauk Medycznych 12/2013, s. 884-890
*Iwona Grabska-Liberek1, Jaromir Wasyluk2, Dorota Derlacka1, Katarzyna Kowalska-Bylak1, Aldona Krzyżewska-Niedziałek1, Urszula Łukasik1, Anna Tręda1
Okulistyka współczesna – obecne możliwości i perspektywy w zakresie diagnostyki i terapii najczęstszych chorób oczu
Contemporary ophthalmology – current possibilities and future prospects regarding diagnostics and management of the most common ophthalmic disorders
1Clinic of Ophthalmology, Medical Center of Postgraduate Education,
Prof. W. Orłowski Independent Public Clinical Hospital, Warszawa
Head of Clinic: Iwona Grabska-Liberek, MD, PhD, assoc. prof.
2Clinic of Ophthalmology, Military Institute of Aviation Medicine, Warszawa
Head of Clinic: prof. Marek Prost, MD, PhD
Zespół autorów z Kliniki Okulistyki Centrum Medycznego Kształcenia Podyplomowego przedstawia osiągnięcia oraz technologiczny postęp w diagnostyce i leczeniu chorób oczu, koncentrując się na najczęściej występujących jednostkach chorobowych i powszechnie stosowanych metodach terapeutycznych. Warto zaznaczyć, że wiele z omawianych procedur jest stosowanych w Klinice CMKP; odział ten posiada szeroką gamę różnych, technologicznie zaawansowanych narzędzi diagnostycznych, wysokiej klasy sprzęt do przeprowadzania zabiegów na przednim i tylnym odcinku gałki ocznej, aparaturę do laseroterapii i chirurgii plastycznej oka. Zwyrodnienie plamki związane z wiekiem, makulopatia i retinopatia cukrzycowa oraz jaskra są głównymi przyczynami nieodwracalnej utraty ostrości widzenia w krajach rozwiniętych powyżej 50 roku życia. Z powodu alarmujących danych statystycznych powyższe choroby stanowią istotny temat badań klinicznych. Główne zainteresowanie stanowią przyczyny progresji, ale przede wszystkim profilaktyka. Chirurgia refrakcyjna zaś to bardzo dynamicznie rozwijająca się gałąź okulistyki. Techniki stosowane obecnie pozwalają na korekcję nawet bardzo wysokich wad refrakcji. Rokrocznie wprowadzane udoskonalenia umożliwiają dalsze rozszerzenie wskazań do tego typu zabiegów oraz zwiększają przewidywalność i bezpieczeństwo stosowanych procedur.
The team of the Ophthalmology Clinic of the Medical Center of Postgraduate Education (MCPE) presents the achievements and technological progress in diagnosing and treatment of the ophthalmic disorders, focusing on the most prevalent diseases and popular therapeutic areas. It is worth mentioning that many of the described procedures are performed in the Ophthalmology Clinic of the MCPE; the department has various and technologically advanced diagnostic tools, high class surgical equipment for microsurgery procedures in the anterior and posterior segments of the eye, devices for laser therapy and oculoplastic surgery. Age-related macular degeneration, diabetic maculopathy and retinpathy and glaucoma are the predominant cause of irreversible blindness in people over 50 in the developed countries. Because of its alarming statistics, these diseases are taking the leading position as a subject of clinical trials in ophthalmology in terms of restraining the progression and, first of all, preventing the onset. Refractive surgery is a rapidly developing branch of ophthalmology. Currently used techniques allow for correction of even a very high refractive errors. Improvements introduced each year allow further expanding of indications for such treatment; also increase the predictability and safety of surgery.
Many people say: “Impressive is the progress in medicine over the last years!”. It might seem to be a truism, however the above sentence fits perfectly for ophthalmology – the field of medicine, which has changed its face completely in the recent times.
The changes proceed in two directions: first, in terms of therapeutic methods, ophthalmology progressively evaluates from a conservative into surgical discipline of medicine, with common use of surgical procedures, laser therapy, and other invasive techniques, including intravitreal injections. From another point of view, thanks to the introduction and popularization of laser scanning – based devices, the eye’s tissue microstructure has been revealed for visualization, qualitative and quantitative assessment, digital documentation and follow-up in the case of any pathology.
The article presents the achievements and technological progress in the diagnosing and treatment of the ophthalmic disorders, focusing on the most prevalent diseases and popular therapeutic areas, such as:
– age-related macular degeneration,
– refractive surgery,
– vitreo-retinal surgery,
– oculoplastic surgery.
The molecular diagnostic techniques have developed rapidly over the last decade, what made it possible to identify the genes and their mutations leading to genetic diseases, and facilitated classification of the diseases according to the genotype. The progress in genetic techniques gives rise to the availability of diagnostic tests, enables screening for hereditary eye disorders and prognosis as to the vision; it also gives hope for treatment. The use of genetic therapy is the future arms to fight diseases with the genetic background.
Hereditary retinal and choroideal dystrophies are the most common and most severe inherited eye disorders. They lead to partial or even total blindness. Retinitis pigmentosa, Leber congenital amaurosis, congenital stationary night blindness, Stargardt disease, and hereditary retinoschisis are the most prevalent dystrophies. 46 genes and 2497 mutations associated with hereditary retinal and choroideal dystrophies have been identified up till now (1).
In the last years effectiveness and safety of the gene therapy in Leber congenital amaurosis has been drawing researchers’ attention (2-4). The autosomal recessive disease that impairs vision in newborns and toddlers is a form of hereditary retinal dystrophy (5). Mutation in the RPE 65 gene is associated with the most severe course of the disease, with serious impairment of vision at birth and loss of vision in the third decade of life. The gene codes a specific protein of the retinal pigment epithelium (65-kD), participating in the regeneration of rhodopsin following exposition to the light (3). In the disease it is possible to keep the functional visual acuity in childhood; it was suggested that the death of photoreceptor takes place in later stages of the disease (6). Transposition of the gene to the place of its action could improve the functioning of the eyes or preserve the remaining vision (3).
Recombined adeno – associated virus (AAV) is used as a vector carrying human’s genetic material into the cells of the eye (3, 4). In vitro AAV induces synthesis of the protein encoded by the RPE 65 gene. In animal models with mutation in the gene, improvement of the retinal function and visual acuity was achieved after subretinal injection of the recombined AAV (7). Maguire et al. reported improved pupillary light reflex and diminished nystagmus after subretinal injections of AAV in young adults with Leber congenital amaurosis, which confirms an increase in the light sensitivity of the retina, resulting from the application of the gene therapy (4). Future clinical trials are needed, particularly on younger patients, who could benefit by the gene therapy more than adults.
Also worth mentioning is that other common eye diseases like age-related macular degeneration, corneal dystrophies, and high myopia, have a molecular basis; therefore the identification of the causing genes might result in increased effectiveness of treatment of the conditions (8).
Glaucoma is defined as a group of optic neuropathies, leading to characteristic progressive, irreversible loss of the visual field, and in consequence to blindness. According to the data from WHO, the disorder recognized as a social disease, is the first cause of total blindness worldwide. In developed countries it takes the second place in the classification, with age-related macular degeneration (AMD) being the first one.
In the past decades glaucoma was considered dependent on increased intraocular pressure, inducing intense symptoms. Presently it is known that the type of the disease constitutes just a small percentage of all cases, which are more noticeable simply because of the symptoms. However, the majority of the patients with glaucoma have no or just mild symptoms, insidiously damaging the optic nerve and the visual field.
The introduction of new computerized diagnostic techniques, also using laser beams, has been the most important achievement in the recent years. Heideberg Retina Tomograph (HRT) – scanning laser opthalmoscope used for examining topography of the optic disc; GDx – scanning laser polarimeter for measuring the nerve fiber layer of the retina, and multiple computed static perimeters – devices for quantitative examination of the visual field, indicating depth of the decrease in retinal sensitivity. Optical Coherence Tomograph (OCT) is a novel apparatus that not only provides images of the retinal cross-sections with histological quality, but also analyzes nerve fibers. To the list belong also ultrasound – based devices, like pachymeter for measuring central corneal thickness and ultrabiomicroscope, generating very high frequency waves for examining the anterior segment of the eye. Traditional measurements of intraocular pressure with a tonometer placed directly on the eye of a lying patient were superseded by more accurate methods: applanation tonometry at slit-lamp and microprocessor-steered dynamic contour Pascal tonometer, displaying reliable digital results, devoid of most of the artifacts.
Treatment of glaucoma has long been more than just administration of eye drops. Therapy is often extended to treatment with neodymium Nd:YAG (iridectomy, selective trabeculoplasy) or argon laser (trabeculoplasty, irydoplasty) depending on the type of disease. Classical surgical procedures, so-called filtrating, i.e. facilitating the flow of the aqueous humor from the eye, were extended by the possibility to use draining implants, some with post-surgically regulated range of activity. Presently the gene therapy with the use of viral vectors is under investigation, as well as neuroprotective medications, blocking apoptosis (programmed death) of the ganglion cells or anti-glaucoma vaccination, boosting regeneration of the damaged cells.
Age-related macular degeneration
Age-related macular degeneration (AMD) is the predominant cause of irreversible blindness in people over 50 in the developed countries (5). According to the data presented by AMD Association, the number of people affected by AMD is estimated to be ca. 300 million worldwide. In Poland the number reaches 1.2 million, the incidence rate is around 120 thousand per year. Around 1.7% of affected people over 50 years of age get blind, while in patients over 85 years, the rate reaches 18%. The problem is essential not only because of the increasing number of patients, but also because often it concerns people who are still professionally and socially active (5, 9).
The main risk factor of the disease is age. Other unchangeable risk factors are: genes, female sex, Caucasian race, light color of the iris, hyperopia, glaucoma, exudative AMD in the other eye. Smoking, obesity, hypertension, diabetes, history of myocardial infarction or apoplexy, persistent sunlight exposure, wrong dietary habits belong to modifiable risk factors (10, 11).
Two forms of AMD are distinguished: “dry” or “atrophic” and “wet” or “exudative”. The atrophic form is more common, as it constitutes 90% of cases. It is characterized by a gradual decrease in visual acuity over a period of a few months to a few years. Usually it is present in the both eyes, however in a different stage. In the macula drusen, focal changes in the pigment epithelium, redistribution of the pigment are observed. Drusen consists of accumulation of pathological material, originating from the retinal pigment epithelium, they can be confluent and extensive, leading to drusen – associated retinal pigment epithelium detachment. Retinal pigment epithelium atrophy (geographical atrophy) develops in more advanced disease; in the case the fovea is involved, visual acuity may be severely decreased (5, 11).
Exudative form is infrequent, however it is responsible for ca. 90% of severe impairment of vision in the patients with AMD. In this type of AMD choroidal neovascularization develops. The pathological new vessels originate from the choriocpillaris and spread into the layers of retina, damaging its structure. Complications include: pigment epithelium detachment, and intraretinal and intravitreal hemorrhages. Without treatment the disease causes formation of macular scar, permanently and irreversibly impairing vision in a short time (approximately 2 years) (5, 11).
Optical coherent tomography (OCT) and spectral optical coherent tomography (SOCT) are extensively used in the diagnostic of AMD. In the method low-coherence infrared light is employed for imagining the structure of retina and choroid. The examination is non-contact, noninvasive, highly repeatable, and it enables to determine how active the disease is and what the effects of treatment are. Apart from the above technique, examinations involving the use of contrast for displaying pathological vessels and spots of leakage: fluorescein and indocanine digital angiography are also widespread (9).
There is no effective treatment of dry AMD. Management consists in slowing down progression and evolution into the exudative form. Supplementation with drugs containing lutein, zeaxantin and antioxidants, together with zinc and preventing the changeable risk factors proved to be effective for this purpose (12).
The goal of AMD treatment is to slow down the progression and stabilize visual acuity. Unfortunately, improvement in vision can be reached only in some of the patients. Presently, intravitreal injections of anti-Vascular Endothelial Growth Factor (anti-VEGF) antibodies or their fragments is the most widely used therapy. The available anti-VEGF preparations are ranimizubab (Lucentis), bewacizumab (Avastin) and pegaptanib sodium (Macugen) (11).
Photo-dynamic therapy (PDT) is another way of treating AMD. In the method werteporfirin – highly light sensitive substance is introduced into the bloodstream and captured by the pathological new vessels. Laser beams damage the pathological tissue, leaving physiological vasculature intact (5). Attempts are made to use microsurgical vitero-retinal techniques, like neovascular membranes removal or translocation of the macula to a different location in the retina (5, 11).
Because of its alarming statistics, the disease is taking the leading position as a subject of clinical trials in ophthalmology in terms of restraining the progression and, first of all, preventing the onset.
Refractive surgery embraces procedures aiming at changing the refraction of the eye throughout modification of the main components of the optical system of the eye: cornea and/or the lens. The indications include myopia, hyperopia, astigmatism and presbyopia, especially in the patients who do not tolerate or not wish to wear glasses or soft lenses.
LASIK (Laser Assisted in Situ Keratomileusis) is currently the most widely performed refractive procedure (13-15). In this procedure superficial layers of the cornea are dissected to form a flap; the flap can be made with microceratome or femtosecond laser. In the next step the uncovered deep layers of the cornea are modified with excimer laser to eliminate the refractive error of the eye. Afterwards, the flap is repositioned on the top of the cornea. The procedure takes a few minutes and is performed under local anesthesia (in eye drops). The both eyes can be operated simultaneously. The use of “Wavefront” technique enables very precise estimation of aberrations of the optical system of the patient (16). Based on the assessment, the cornea is modeled during the surgery. “Wavefront” is a term describing a surface that connects points in the same phase of light waves. Spotlight produces spherical wavefront. Before it reaches the retina, it is banded and deformed by all the structures of the eye it passes through. Optical aberrations created by every eye are as individual as a fingerprint. Wavefront technique enables not only myopia, hyperopia or astigmatism but also higher-order aberrations to be described and corrected.
Because during LASIK only a thin layer of the tissue is left untouched, there is a risk of ectasia of the cornea. In the Epi-LASIK technique only the epithelium is separated from the cornea with epiceratome, without encroaching corneal stroma (17, 18). After performing laser fotoablation, the epithelium is placed back on the cornea. The cornea is then covered with a soft contact lens until the epithelium heals (3-10 days). Discomfort (tearing, pain) is more pronounced than in LASIK. The method resembles LASEK, but no alcohol is used to separate epithelium (what eliminates its negative influence on the tissues); however, it might be difficult to separate epithelium from the peripheral parts of the flap.
In the SBK-LASIK technique a thin flap consisting of epithelium, Bowman’s membrane and superficial stroma is created with a microceratome (17). Separating a very thin flap, 70-100 microns thick, has the advantage of greater comfort for the patient, short healing time, no risk of complications that appear after classical LASIK (for example dry eye syndrome). There is no need to apply a contact lens after the procedure (while it is necessary after LASK and PRK). The risk of flap – related complications is yet higher than in LASIK.
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