Conjunctivitis and keratitis are accompanied by a decrease in visual function and lead to serious complications in 26% of cases, and in 19% of cases they can even lead to loss of the organ of vision.
The problem of the treatment of inflammatory eye diseases to this day throughout the world remains relevant in the medical and social terms, and the fight against corneal blindness is one of the priorities of ophthalmology . The search for new high-tech methods of treatment in ophthalmology is not always due to satisfactory results of treatment using existing methods. One of these high-tech methods is photodynamic therapy (PDT). The development and introduction of PDT in the treatment of oncological diseases has aroused a wide interest of researchers in the possibility of applying these methods in other areas of medicine and, in particular, in ophthalmology.
The use of PDT in the ophthalmologic practice of Uzbekistan was held back by the high commercial value of foreign laser equipment and photosensitizers (FS). However, in Uzbekistan, there have not yet been any studies devoted to studying the effect of PDT on the optical media and membranes of the eyeball and assessing the possibility of a damaging effect on deep-lying highly differentiated structures of the eye, as well as the use of PDT in the treatment of inflammatory diseases of the ocular surface. At present, our scientists have developed a device for PDT – ALT “Vostok”. The development of safe for the organ of vision doses of radiation determines the effectiveness of treatment of patients with inflammatory diseases of the ocular surface.
The goal is to improve the results of treatment of inflammatory diseases of the ocular surface by developing safe doses and power of PDT on domestic equipment.
Material and methods
A survey of 70 patients with inflammatory diseases of the eye. Of the examined – 40 patients (80 eyes) with conjunctivitis and 30 patients (30 eyes) – with keratitis. Depending on the treatment, two groups of patients were identified: the control (35 patients) and the main (35 patients). The formation of groups depending on the nosology, form of the disease, severity and clinical and functional manifestations was homogeneous.
In the control group, patients with conjunctivitis (20 patients – 40 eyes) were given traditional treatment, including: instillations of 0.3% – nogofloksimeda (2 drops 6 times a day). Patients of the main group – 20 patients (20 eyes), in addition to the above treatment, PDT was performed.
Photodynamic therapy was performed using the ALT Vostok apparatus. Laser radiation was directed to the projection of the eye (aperture of 5 mm) at a therapeutic dose (TD) – 300 mJ, wavelength – 630 nm, pulsed irradiation with an exposure of 3 minutes, previously instilled in the photosensitizer – methylene blue (1% aqueous solution) according to the method developed based on experimental studies (decision of the Committee on Bioethics of the Republic of Uzbekistan No. 23/2 dated May 8, 2014).
30 patients (30 eyes) with keratitis were examined, in all cases the process was one-sided, they were also divided into 2 homogeneous groups depending on the treatment being performed – the control 15 patients (15 eyes) and the main 15 patients (15 eyes), similar in severity , localization, etiology and duration of the process.
Patients in the control group received traditional therapy: putting 0.3% ointment phloximed in the conjunctival sac (4 times a day), instillation of the lungs of mydriatics (2 drops 2 times a day) and 20% gel solcoseryl (1 drop 3 times a day) . In the main group of patients, standard treatment was supplemented with PDT: irradiation at a dose of 300 mJ (630 nm) with a photosensitizer — 1% aqueous methylene blue with a duration of 3 minutes for 10 days.
All patients were prescribed general therapy: antihistamines (suprastin, 1 tablet 1 time per day), group B vitamins (vitamin B complex 2.0 v / m). All patients underwent a clinical-functional study (external examination of the eye, examination under focal illumination, visometry, biomicroscopy, ophthalmoscopy), bacteriological studies of the scraping from the conjunctival cavity.
Microbiological studies have shown that staphylococcus hemolytic (26.4%) were the most common causative agents of the infectious process, 17.2% were less likely to be epidermal, and 16.4% were golden. Mixed etiology was observed in 39% of cases, with the combination of staphylococci, including pyogenic, diphtheroids, micrococci, Candida, in rare cases of E. Coli, as well as fungi. As a result of the treatment, there was noted the absence of microflora in the main group in patients with conjunctivitis for 2–3 days, in the control group – for 5–7 days. In patients with keratitis of the main group, the pathogenic microflora disappeared in 3-4 days, in the control group of patients – in 7-8 days.
In patients with conjunctivitis, initially, in both groups, inflammation corresponded to extremely high values of the inflammatory process. At the same time, the average degree of inflammation was noted in 14 (82.3%) and in 12 (70.6%) examined patients of the control and main groups, whereas in 3 (17.7%) and 5 (29.4%) patients accordingly, severe inflammation was noted. In the control group of patients receiving standard antibacterial treatment, the index of the severity of inflammation decreased by the 3rd day of treatment by 1.36 times (p <0.05), in 11 (64.7%) patients an average was observed, in 6 (35, 3%) – mild inflammation. Subsequently (on the 7th day of treatment), the inflammation index decreased significantly 2.17 (p <0.001) times compared to the previous term, and in all examined patients a slight degree of inflammation was noted. By the final examination period, 5 (29.4%) patients had mild inflammation.
In contrast to the control group of patients, in the main group of patients treated with PDT, the index of the severity of inflammation decreased by the 3rd day of treatment by 2.62 (p <0.001) and 1.88 (p <0.001) times relative to baseline parameters and control values group at the same time. In all patients of the main group, we noted a mild degree of inflammation. Subsequently (on the 7th day of treatment), the index of the severity of inflammation significantly decreased – more than 10 times (p <0.001), and only 2 (11.8%) patients had a mild degree of inflammation. By the final examination period in all patients, the inflammatory process was stopped. In our opinion, this is due to the pronounced antibacterial effect of photodynamic therapy, which caused regression of the inflammatory process, accelerated reparative processes, increased resorption of edema and conjunctival infiltration.
By the 7th day of the course of treatment, further positive clinical dynamics were noted. The total duration of treatment in the main group in patients with conjunctivitis decreased by 1.84 (p <0.01) times as compared with the control. At the same time, no general and local toxic-allergic reactions were identified when using PDT. Indicators of initial data of visual acuity in patients with conjunctivitis in all groups ranged from 0.7 to 1.0 with correction.
In the control group of patients with keratitis who received standard antibacterial treatment and reparative regeneration stimulants, the severity index of inflammation decreased by the 3rd day of treatment by 1.17 times. Subsequently (on the 7th day of treatment), the inflammation index decreased significantly by 2 times, and by the final examination period – by 3.94 (p <0.001) times compared to the previous study dates, mild inflammatory events were detected in 6 (40%) patients.
PDT reduced the severity index of inflammation on the 3rd day of treatment by 2.17 (p <0.001) times relative to baseline parameters and 1.81 (p <0.001) times compared to the control group. Subsequently (on the 7th day of treatment), the inflammation index decreased significantly in 2.67 (p <0.001) and 2.52 (p <0.001) times compared to the previous study period and indicators of the control group, respectively. By the final date of the proposed therapy, inflammation was absent in all treated patients, whereas in the control group, mild inflammation remained in 40% of the treated patients.
In the main group of patients with keratitis, on the first day after the start of treatment, the intensity of the corneal syndrome decreased, which was manifested by a decrease in photophobia, lacrimation, ciliary pain, patients felt significant relief.
In the main group of patients with keratitis, the disappearance and decrease in the intensity of the pericorneal and vascular injection of the eyeball occurred on the 4–5th day from the start of treatment. In the control group, the disappearance of the above symptoms occurred more slowly. Cessation of discharge – by the 8th, the disappearance of corneal syndrome and pericorneal injection – by the 9th day. The resorption of edema and infiltration of the corneal tissues surrounding the defect in patients of the main group led to a rapid restoration of its transparency; by the 4–5th day, the cornea defect was completely covered with a layer of epithelial cells (in the control – on the 8–9th day), and by the 5th day, the resorption of infiltrates occurred (in the control – on the 8–9th day). Different periods of relief of the inflammatory process in the groups were reflected in the terms of treatment: in the main this indicator was 5.4 ± 0.42 bed-days (p <0.01), in the control one – 8.9 ± 0.4.
In the groups where PDT was used, complete epithelialization of the cornea was noted without any impairment of its transparency in 13 (86.7%) patients with superficial keratitis. In the formation of corneal opacities, vascularization was absent or was weak. At the same time, in the overwhelming majority of the eyes of the control group, corneal vascularization did not tend to reverse development, the intensity of corneal opacities was higher: restoration of cornea transparency was observed in 3 (20%) patients, which is 3.42 (p <0.001) times less indicators of the main group, the presence of cloudy turbidity or “spots” was observed in 80% of cases, which is 2.53 times (p <0.001) more than in the main group.
Indicators of visual acuity in 30 (30 eyes) patients with keratitis varied from 0.1 to 0.9.
In stromal keratitis, visual acuity was significantly reduced due to edema and corneal opacities. Visual acuity below 0.6 in patients in the control group was recorded in 6 eyes, in the main group – at 8, which was, respectively, 40% and 43.3%, above 0.6 – at 8 (60%) and 7 (46.7%) eyes, respectively.
An increase in OZ during keratitis in the main group by more than 0.1–0.2 was observed in 13.3% of cases. In contrast to the indicators of the control group, in the main group, patients noted a significant increase in visual acuity on the 4-5th day of treatment: in 26.7% of OZ increased by 0.2-0.3, in 40% – by more than 0, four. So, the analysis of the OZ dynamics indicates that the effectiveness of complex treatment of patients using PDT is higher than in the group of patients treated with the standard method.
PDT using a photosensitizer – methylene blue in the developed doses and power has a positive epithelial and bacteriostatic effect on the processes of repair and regeneration in inflammatory diseases of the ocular surface. The proposed complex treatment causes an improvement in the clinical picture of conjunctivitis and superficial keratitis, manifested by a decrease in inflammatory infiltration and increased corneal epithelialization.
The use of photodynamic therapy according to the developed scheme contributes to increasing the effectiveness of treating inflammatory diseases of the ocular surface: accelerating tissue regeneration on the 5-6th day, restoring transparency of the cornea in 86.6% of cases, increasing visual functions in 86.7% of cases and reducing the treatment time to 5–6 days