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National Journal glaucoma

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Vol 17, No 1 (2018)
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ORIGINAL ARTICLES

3-13 1865
Abstract

PURPOSE: To identify the lymphatic structures of the human eye, study their ultrastructural organization and morphological changes in the ciliary body and the choroid in patients with primary open-angle glaucoma.

METHODS: Fragments of eye tissues enucleated for medical indications (n=28) were studied. The main group included 17 eyes of patients diagnosed with terminal stage primary open-angle glaucoma. The tissues underwent an immunohistochemical study using monoclonal antibodies to markers of the following agents: blood vessel endotheliocytes CD31 and CD34 («Novocasra», Germany), lymphatic endotheliocytes LYVE-1 («Abcam», England), Podoplanin («Monosan», The Netherlands) and Prox-1 («Covance», Germany), fibroblast growth factor receptor marker FGFR («Abcam», England). Obtained eye tissues were studied by means of Leica DME light microscope. Electron microscopy of the eye tissues was carried out using JEM 1400 electron microscope (Japan).

RESULTS: The imunohistochemical and ultrastructural analysis of the ciliary body revealed the presence of lymphatic channels and structured interstitial spaces (tissue slits) formed by collagen fibers and fibroblasts. Lymphatic canals and lacunae were also found in the choroid. Lymphatic channels were located in the vascular capillary layer and were confined to cells similar to fibroblasts and pigment cells, while lymphatic lacunae were found in the suprachoroid layer and were lined with cells similar to fibroblasts. For the first time lymphatic structures were found on the border between the sclera and the lamina cribrosa and in the optic nerve sheath. The ciliary body in patients with terminal primary open-angle glaucoma shows the following structural signs of edema and stromal swelling: interstitial space widening, venous vessels lumen enlargement, reduction of the lymphatic endothelial cells marker expression. Similar processes were found in the choroid during the terminal stage of primary open-angle glaucoma: enlarged blood and lymphatic vessels lumens, pericapillary spaces swelling and enlargement, choriocapillary layer stroma swelling as well as the disruption of the anchoring collagen fibrils binding to myofibroblasts and pigment cells. The study revealed an associated with swelling significant increase in choroid thickness and volume density of the epithelium, interstitial spaces and vessels, which indicated inflammation.

CONCLUSION: The new fundamental data obtained during the study broadens the current understanding of lymphatic system elements presence in the human eye and their changes associated with primary open-angle glaucoma. This allows us to postulate the existence of a lymphatic (uveolymphatic) pathway of intraocular (tissue) fluid outflow, aimed at utilizing and excreting metabolic and cellular destruction products. Structural disturbances of the lymphatic outflow components play an important role in the mechanisms of primary open-angle glaucoma development.

14-28 999
Abstract

PURPOSE: To determine the effect of some IOP level indicators on disease progression in patients with primary open-angle glaucoma.

METHODS: This combined, analytical scientific and clinical multicenter cohort study was conducted between January and April 2017. A total of 136 participants (237 eyes) from 30 academic referral centers from 6 (six) countries (Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russia, Uzbekistan) were enrolled — 52 (38.2%) males and 84 (61.8%) females. As a first step, glaucoma anamnesis and all treatment strategies were retrospectively evaluated. Glaucoma was diagnosed according to the differential diagnosis system and confirmed by special methods in all cases. All data concerning the stage of disease were verified repeatedly at the start of the study according to the current glaucoma classification and with additional IOP measurements (Maklakov tonometer, 10 g), morphometric and functional indicators research.

RESULTS: The history of the disease at the time of the final examination for patients with different stages of glaucoma was comparable in time and averaged 4.3 (3.7, 5.8) years. Over the average follow-up period, the initial stage did not progress in 73.37% of mild glaucoma cases, 19.02% of cases have progressed to moderate glaucoma, 4.35% have progressed to advanced glaucoma, 3.26% — to terminal glaucoma. Moderate glaucoma stage was preserved in 59.52% cases, in 33.33% it progressed to advanced glaucoma, in 7.15% — to terminal glaucoma. Advanced glaucoma stage remained without a progress in 54.55% cases, in 45.45% cases it has progressed to terminal glaucoma during 5 years. Mean IOP level after follow-up period was 19 (17; 21) mm Hg and had no significant difference (p=0.557, H=2.073). Consequently, only in early-stage glaucoma cases the average «inter-visit» IOP value corresponded with values recommended as a target IOP by the Russian Glaucoma Society, whereas in other cases (moderate and advanced glaucoma) it was significantly higher. There was no significant difference (p=0.597, H=1.882) between «optimal» IOP-level in patients with different glaucoma stages, and «intolerant» IOP-level increased from stage to stage (p<0.001, H=32.175). The initial regimen was generally effective for patients with mild glaucoma with IOP level increase registered only in 2.17% cases. «Inter-visit» IOP-level was above recommended values in 38.1% cases in patients with moderate primary open-angle glaucoma, and in 81.82% in patients with advanced primary open-angle glaucoma. The analysis of visual field change during the follow-up period showed that MD increased in 29.5% cases and decreased in 70.5% cases.

CONCLUSION: In this paper we assessed IOP level not only using classical methods, but also introducing new terminology, such as the «inter-visit» IOP-level, the «optimal» IOP-level, the «intolerant» IOP-level, to characterize the IOP dynamics in different time intervals. The results of the study suggest that inter-visit IOP range can be one of the possible predictors of glaucomatous damage, and therefore can be useful for correction of existing clinical guidelines.

30-35 764
Abstract

PURPOSE: To analyze the corneoscleral biomechanics changes in patients with latanoprost instillations compared to local beta-blockers therapy by means of bidirectional applanation tonometry.

METHODS: The study included 2 groups of patients with newly diagnosed primary open-angle glaucoma: the Main group comprised 320 patients (320 eyes), the Control group — 200 (200 eyes). To assess the fibrous tunic viscoelastic properties the patients underwent bidirectional applanation tonometry using Ocular Response Analyzer (ORA, «Reichert»,USA).

Patients of the Main group received hypotensive latanoprost 0.005% (Prolatan, «Sentiss») instillations once daily in the evening, while the Control group received timolol maleate 0.5% solution twice daily with a 12-hour interval. Corneoscleral biomechanics was monitored prior to instillations administration and 6 months after to assess the dynamics and the treatment effect. The study included only one eye of each patient.

RESULTS: Patients of the Main group treated with latanoprost 0.005% showed an average IOP decrease by 33% with an equal change in both parameters measured with bidirectional applanation tonometry. Corneal resistance factor (CRF) decrease was accompanied by corneal hysteresis (CH) increase, equaling the parameters, which in turn indicated the fibrous tunic normal condition recovery. Similar changes in biomechanical parameters in the control group were expressed to a lesser degree leaving a discrepancy between CRF and CH levels.

CONCLUSION: The fibrous tunic of the eye showed no significant changes during latanoprost therapy. Biomechanical parameters dynamics measured by bidirectional corneal applanation was mostly related to IOP decrease. The effect of latanoprost on cornea and sclera was more pronounced, which can possibly be attributed to the difference in hypotensive efficacy between latanoprost and timolol maleate.

37-42 695
Abstract

The most frequent cause for glaucoma surgery failure apart from the progression of dystrophic changes in the eye’s drainage system is morphological changes in connective tissue structures that increase the risk of scarring at the operation site. Since currently available preventive measures, that are either based on medically affecting the wound healing process (e.g. metabolic antagonists) or method improvements, do not always give the intended result, there are also other directions of glaucoma research, one of which focuses on the application of drainage devices and systems. PURPOSE: to study the efficacy and safety of iGen drainage device in primary open-angle glaucoma surgery.

METHODS: The study group included 35 male and 51 female patients aged 55 to 79 years (mean age 65.9±9 years). All the patients of the study group (86 patients, 86 eyes) underwent an iGen drainage device implant. Among the patients, 37 (43.1%) had stage II glaucoma, 49 (56.9%) — stage III. Intraocular pressure (IOP) was moderately elevated in 52 patients (60.5%) and significantly elevated in 34 patients (39.5%). Mean IOP prior to the operation was 34.6±9.2 mm Hg with the minimum of24.7 mm Hg and the maximum of56.5 mm Hg.

RESULTS. One week follow-up showed mean IOP levels of 15.1±11.3 mm Hg. At day 30 of the post-surgical followup, IOP in the study group increased by 2–3 mm Hg and in average amounted to 17.8±6.4 mm Hg. Further observation showed no IOP increase, and at 12 months it equaled 18.8±2.3 mm Hg. Absolute success of iGen implantation was accomplished in 37 (42.9%) patients. Qualified success (IOP normalization without additional antihypertensive therapy + IOP normalization with additional antihypertensive therapy by 1.8 medications in average) was achieved in 71 (82.1%) patients. Complications frequency and characteristics depended on the initial clinical status and included ciliochoroidal detachment (10.4%), hyphema (10.4%), transient hypertension (1.2%).

CONCLUSION: The choice of explant drainage in repeated glaucoma surgery depends on predominant localization of cicatricial blockade of the outflow tracts created during previous surgeries. In cases when conjunctival-scleral adhesions served as the obvious cause of the surgery failure, iGen collagen drainage is preferable as having integral success rate of 82.1%.

43-53 889
Abstract

PURPOSE: Analysis of the mediumand long-term results of the mini-shunt Ex-Press implantation in glaucoma surgical treatment.

METHODS: Non-penetrating deep sclerectomy with the mini-shunt Ex-PRESS R-50 implantation was performed in 198 eyes of 177 patients with uncontrolled and/or refractory glaucoma between 2011 and 2014. Exclusion criteria for patients: signs of neovascularisation, close-angle or congenital glaucoma, previous ophthalmologic surgeries during the last 6 months, the need for simultaneous combined cataract and glaucoma surgery. The study included 161 patients (176 eyes). A review of the patients’ anamnesis revealed a history of previous glaucoma surgical procedures in 126 (77.6%) patients, cataract phacoemulsification with IOL implantation in 108 (67%) patients and vitrectomy in 43 (26.7%) cases. All surgical interventions were undertaken within a period of more than 6 months before the present study. A standard ophthalmologic examination was performed in all patients prior to surgery and on days 1 and 7, as well as 1, 2, 3, 6, 12, 18, 24 and 36 months after the drainage implantation. In a number of patients, examinations were also performed 48 (n=44, 27.3%) and 60 (n=21, 13%) months after the operation. In addition, patients were divided into group I («phakic» glaucoma, n=53; 32.9%) and group II (pseudophakic glaucoma, n=108; 78.3%)

RESULTS: The mean follow-up period was 43.7±2.9 months. The mean age of patients at the time of surgery was 72.4 ± 9.6 years, with 63 (39.1%) male and 98 (60.9%) female patients. IOP decrease compared to preoperative values of 32.3±8.7 mmHg amounted to 6.2±7.7 mm Hg after 1 week, 11.9±5.8 mm Hg after 1 month, 12.5±4.0 mm Hg after 2 months, 12.7±4.8 mm Hg after 3 months, 12.1±4.5 mm Hg after 6 months, 11.7±4.2 mm Hg after 12 months, 12.9±5.1 mm Hg 18 months after surgery. At the follow-up period of 24 months, the IOP decreased to 15.3±6.6 mm Hg, and at follow-ups of 36 months to 17.5±6.8 mm Hg (45.8%). In 44 (27.3%) patients 48 months later, the IOP level exceeded the compensation level with average values of 22.4±8.0 mm Hg. In 60 months after the operation 21 (13%) patients had a mean IOP level of 26.1±8.2 mm Hg. A statistically insignificant change in BCVA from 0.61±0.25 in the preoperative period to 0.57±0.31 during the last examination was observed (p>0.1). There was a significant decrease in the number of glaucoma instillations with the average numbers of 0.55±1.1 and 0.89±1.2 24 and 36 months after the surgery respectively, compared to 2.7±0.9 prior to the surgery (p=0.002 and p=0.01). In all the investigated cases, a daily massage of the filtration zone was performed during the postoperative period. In 94 (58.4%) patients, the IAG laser procedure was performed on the shunt at various postoperative times. Postoperative complications included a transient hypotension in the early (10-14 days) postoperative period, Seidel’s symptom and bleb encapsulation, which required additional intervention. At the maximum follow-up period of 36 months, somewhat better results were obtained in group II (mean IOP 15.9±4.2 mm Hg vs. 17.3±4.4 mm Hg in group I, p>0.1). Similar differences were obtained for the number of glaucoma drugs taken (0.81±0.9 in group II against 0.97±1.1 in group I, p>0.1). Larger differences were obtained for BCVA during the long-term follow-up period (0.62±0.26 in group II versus 0.38±0.21 in group I, 0.05<p<0.1).

CONCLUSION: Ex-PRESS mini-shunt implantation is indicated in patients with refractory glaucoma when with previous interventions and maximum antihypertention regimen proved insufficient to compensate intraocular pressure level. Relative simplicity of the implantation technique, a small percentage of complications and a high efficiency in the medium term observation period make it possible to recommend the use of this device for wide ophthalmic surgical practice. Optimal results are possible with the implantation of a mini-shunt under the superficial scleral flap and a special mode of postoperative management of the patient, which allows to maintain the functioning of the shunt and to provide a tolerant intraocular pressure. Implantation of the mini-shunt Ex-PRESS R-50 in patients with pseudophakia results in slightly better but statistically insignificant functional results, however, due to the reduction in the effect in long-term (up to 5 years) follow-up, this surgical intervention is not an operation of first choice for this group of patients.

55-69 757
Abstract

OBJECTIVE: To study the features of structural and functional characteristics in patients with primary openangle glaucoma (POAG), pseudoexfoliation glaucoma (PEG) (including the fellow eye without glaucoma) and ocular hypertension (OH).

METHODS: At the onset of the disease we analyzed the average intraocular pressure level; the average retinal photosensitivity deviation (MD) and the standard photosensitivity deviation (PSD), measured in the course of threshold perimetry. At the time of inclusion in the study the patients underwent visometry, tonometry, elastotonometry, computer perimetry, optical coherence tomography, pachymetry (Spectralis OCT, “Heidelberg Engineering”, Germany), kerato-refractometry, orbital vessels ultrasound dopplerography (USDG) (data will be presented in the second part of the publication).

RESULTS: Taking into account the patients’ age, we noted a statistically significant increase of the retinal fiber nerve layer (RFNL) thickness only in the «PEG-» group compared to POAG and PEG, with no significant differences from the OH and norm groups, which fully agrees with the functional differences (MD) obtained by groups. Thus, the observation groups are comparable in terms of their structural characteristics, and it is consistent with the generally accepted changes at the initial stage of glaucoma.

CONCLUSION: Structural and functional changes at the initial stages of POAG and PEG are quite comparable with normal and OH patients, moreover in the «PEG-» group we observed the most prominent invariability of structural and functional characteristics. Thus, at the initial stage of the pathological process, the structural and functional characteristics cannot serve as reliable markers in diagnosing and predicting the development of glaucoma process, which is especially important for patients with OH and PEG-.

70-74 799
Abstract

The article describes the development of ophthalmology during the period of independence of the Republic of Tajikistan. Due to an update of the normative legal base of the ophthalmologic service, and efforts to optimize and modernize the material and technical base that existed in the 1990s, reorganize the service of specialized care in polyclinics and hospitals at all levels, today the ophthalmic care will be provided in all eye institutions of the country, including primary health care at the level of the rural health center and the high-tech medical care at the tertiary level. The introduction of new methods of diagnosis, treatment and surgical interventions, especially in the field of vitreoretinal, ultrasound and laser surgery, significantly reduced the number of patients leaving to other regions for treatment. The introduction of minimally invasive surgery minimized the number of complications during surgery, significantly reducing the average duration of the patient’s stay at the hospital and simultaneously improving the occupancy rates of ophthalmologic beds in the republican institutions, which for the last 5 years accounted for approximately 91% of the total.

Thus, the improvement methods of diagnosis and treatment of eye diseases aimed at enhancing the effectiveness of ophthalmic care for patients is associated with the development of microsurgical techniques, bed capacity optimization, material and technical base modernization and human resources strengthening and with the beginning of a new stage in the development of high-tech ophthalmology service it requires the development of a new ophthalmic care program, economically and clinically acceptable for the Republic of Tajikistan, as a developing country.

75-84 799
Abstract

PURPOSE: To test and compare the relative prevalence of primary vascular dysregulation (PVD) symptoms in randomly selected population group in Russia.

METHODS: Subjects of randomly selected population group of Moscow and Moscow region filled out a questionnaire containing 15 questions related to signs and symptoms of primary vascular dysregulation (159 people: 90 male; 69 female).

RESULTS: In Russian population the most frequent symptoms are the following: low blood pressure; reduced sense of thirst; increased sense of smell; a tendency toward perfectionism; a long sleep onset time. From the literature we know that predominant symptoms differed in Russian population from those in Korean and Swiss populations (depending on geographical area).

CONCLUSION: Data on PVD signs and symptoms prevalence in Russia and was obtained. The relative frequency of different PVD signs and symptoms in randomly selected average population varies between different countries. Therefore; if the diagnosis of PVD is based on patients’ self-reported signs and symptoms; they should be compared to general prevalence of signs and symptoms in relevant population.

86-100 1227
Abstract

PURPOSE: To study the efficacy and safety of “Longidaze® lyophilsate for solution for injections 1500 IE” in subconjunctival injections for wound healing regulation after glaucoma surgery.

METHODS: 90 patients (90 eyes) with primary openangle glaucoma, demanding repeated trabeculectomy, were enrolled into study. Average baseline IOP was 28.7±9.8 mmHg, average amount of hypotensive drugs was 2.6±0.5. All the patients underwent primary trabecu-lectomy in the course of last 6 months.

Patients were randomized into 3 groups: group 1 received one Longidaze® injection 7 days after trabeculectomy; group 2 received 2 Longidaze® injections — 7 and 14 days after trabeculectomy respectively; group 3 received common antiinflammatory postoperative treatment (dexamethasone and tobramycin fixed combination (“Tobradex”) and nepafenac solution (“Nevanak”) 4 times daily for 1 month).

Before the operation, and 6 and 12 months after visometry, static perimetry and confocal retinal tomography were performed. In 1 day, 1 week, 1, 3, 6 and 12 months after the operation tonometry, hemoglobin saturation (SO2) assessment and computerized evaluation of filtration zone hyperemia were performed.

RESULTS: On the first day after trabeculectomy the SO2 level decreased approximately by 1/3 in all groups with a significant difference between groups 1 and 3 (р=0.0166), showing a recovery trend in 1 week. In group 2 SO2 level had been decreasing since month 1 till month 3 after trabeculectomy. The SO2 difference between groups during the other periods wasn’t statistically significant.

By the end of the first month after the surgery hyperemia level in group 1 decreased from 27.3±4.3 to 23.5±4.4%. A repeated injection in group 2 maintained hyperemia at the initial level. In the control group hyperemia level decreased significantly from 26.9±4.5 to 18.1±3.2% (the difference between groups is significant in all cases). A significant decrease of hyperemia (11.9±3.2, 11.5±3.6 and 12.0±3.4%) occurred by month 3 without any significant difference between groups, with overall hyperemia level returning to normal by month 6.

The filtering bleb assessment according to the Wuerzburg bleb classification score revealed the indices’ normalization by the end of the first month after trabeculectomy with a significant advantage in groups 1 and 2 (9.52±1.48 and 9.15±1.67; 8.53±1.83 incontrol group), maintaining the trend during the first year.

IOP level didn’t differ in the groups till month 3. By month 6 IOP level in the control group increased by 1.1-1.3 mmHg without significant difference.

Absolute trabeculectomy success (reaching target IOP without hypotensive drugs and needling) equaled 82, 81 and 70% in groups 1, 2 and 3 correspondingly. Qualified trabeculectomy success with postoperative use of needling and hypotensive therapy appeared to be comparable, equaling 86, 84 and 87%. Complications rate didn’t differ significantly between the groups.

CONCLUSION: The study results confirm a high level of injury associated with repeated trabeculectomy. Both single and repeated Longidaze® injections didn’t significantly affect the oxygen metabolism in the filtration zone. Longidaze® injection slightly slowed the decrease of hyperemia, which appeared in the control group 1 week after the surgery. A significant negative linear dependency between SO2 level and filtration zone hyperemia was detected in all groups, revealing a close connection between hyperemia level and oxygen consumption by the tissues.

According to the Wuerzburg bleb classification score, blebs characteristics in groups 1 and 2 during the follow-up period exceeded those of the control group. No significant difference between 1 or 2 injections was noted in terms of IOP change.

Subconjucntival LongidazeR injections generally do not affect the postoperative complications rate, related to trabeculectomy.

 

REVIEW OF LITERATURE

101-112 1107
Abstract

The review presents the results of clinical studies, which suggest that ocular hemodynamics disorder can be one of the triggers of glaucoma development and progression. While the fact that vascular disorders are primary in glaucoma still has not been proved, there is a working concept admitting their role in glaucoma pathogenesis. It includes a theory of venous dysfunction, primary vascular dysregulation and biomechanical disorders at the scleral membrane level. In glaucoma there is an increase in pulsatile venous pressure, and the lack of central retinal vein pulsation is an unfavorable prognostic. Glaucoma pathogenesis has some common features with retinal vein occlusion: both are characterized by vascular dysregulation, not only in arterial, but also venous bed. Occlusion of the scleral membrane’s capillaries weakens both the membrane and axons passing through it. Since the problem of circulatory disorders in glaucoma is still under discussion, currently there are no definitive treatment recommendations aimed at improving ocular hemodynamics in this disease. Taking into account that the ocular blood flow autoregulation is active in a wide range of IOP and perfusion pressure conditions, prescribing vasoactive drugs in order to improve the ocular blood flow is questionable.

113-116 702
Abstract

Open-angle glaucoma pathogenesis, which is important for early diagnosis, treatment and prevention of the disease, remains one of the most difficult and important problems of ophthalmology. A significant role in solving this problem belonged to Kuibyshev Glaucoma Research Laboratory, one of the main directions of which was to study the role of connective tissue in primary open-angle glaucoma pathogenesis.

The purpose of this work is to conduct a retrospective analysis of comprehensive morphological studies of the nature of changes in connective tissue of both anterior segment (drainage system) and the posterior segment (optic nerve) performed in the Glaucoma Research Laboratory.

It is noted that growing disorganization of eye drainage system’s connective tissue components, which happens due to glaucoma, is a cause of disturbance of the intraocular fluid circulation. A similar pattern is noted in the connective tissue components of the cribriform plate. The decrease in the density of the connective tissue of the cribriform plate at the beginning of the glaucoma process and thinning of the cribriform plate in later stages are critical signs of changes in connective tissue supporting the optic nerve. The study of the choroid microvasculature in glaucoma showed that the changes in the vessels are secondary to the connective tissue pathology.



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ISSN 2078-4104 (Print)
ISSN 2311-6862 (Online)