The PreserFlo MicroShunt in the Context of Minimally Invasive Glaucoma Surgery: A Narrative Review.

Recently, the quest for novel glaucoma surgical techniques and devices has been underway. Trabeculectomy remains the gold standard, but it requires the implantation of glaucoma drainage devices and frequent follow-ups, and it also carries a high risk of serious complications. The need for less invasive and safer procedures has led to the development of minimally invasive glaucoma surgery (MIGS), particularly for patients with mild-to-moderate disease. Among them, minimally invasive bleb surgery seems to be effective in classical glaucoma surgery, while maintaining MIGS benefits. The relatively new PreserFlo® MicroShunt (Santen, Osaka, Japan) is registered in Europe. It was released in 2019 for the treatment of patients with early-to-advanced open-angle glaucoma, where intraocular pressure (IOP) remains uncontrolled while on maximum tolerated medication and/or where glaucoma progression warrants surgery. This review focuses on the place of the PreserFlo MicroShunt, characterized by ab externo implantation, among MIGS procedures, discussing its advantages and disadvantages. The mechanisms of action, technical aspects, efficacy, and safety issues are summarized. The surgical technique, its efficacy, and safety profile are described, and directions for future studies are indicated. The PreserFlo MicroShunt ensures a high safety profile, minimal anatomical disruption, meaningful IOP-lowering effect, and ease of use for patients and physicians.

Early Complications and Results of Preserflo MicroShunt in the Management of Uncontrolled Open-Angle Glaucoma: A Case Series.

We analyze the surgical outcomes and early complications with their management of the Preserflo MicroShunt (Santen Pharmaceutical Co., Ltd., Osaka, Japan) at six-month follow-up. The study is conducted between March 2021 and May 2022. Best-corrected visual acuity (BCVA) logMAR, intraocular pressure (IOP), and changes in glaucoma medications are assessed. Thirty eyes of 30 patients (22 women [73.3%] and 8 men [26.7%]) are included. They are augmented with mitomycin C (MMC) 0.5 mg/mL (8 subjects) or MMC 0.2 mg/mL (22 subjects) intraoperatively. BCVA is significantly higher one day after the treatment than before the treatment (MD with 95% CI = 0.05 (<0.01; 0.30); p = 0.045) when analyzing all patients. Such dependency is not observed when analyzing only patients treated with MMC 0.2 or 0.5 mg/mL (p > 0.050 for both analyses). No other statistically significant differences are detected in the level of BCVA before and after treatment. Among the patients, overall IOP is significantly lower at each time point after treatment than before surgery (p < 0.001 for all analyses). Among patients augmented with MMC 0.2 mg/mL, the IOP level is also significantly lower at each time point after treatment than before treatment (p ≤ 0.001 for all analyses). The same differences are observed among patients with MMC = 0.5­the IOP level is significantly lower at each time point after treatment than before treatment (p < 0.050 for all analyses). Five subjects (16.7%) require anti-glaucoma medications three months after the procedure. Early complications (hypotony, choroidal effusion, keratitis, hyphema, and bleb fibrosis) are observed in 46.7% of cases. Our early results show that Preserflo MicroShunt is safe and effective for lowering IOP; however, it is not free from transient complications.

The expressions of Fas and caspase-3 in human glaucomatous optic nerve axons.

BACKGROUND: Glaucoma is a chronic neurodegeneration of the optic nerve and one of the leading causes of vision loss in the world among the aging. Recent data suggest an important role for Fas receptor- and caspase-3-mediated apoptosis in the pathophysiology of glaucoma. In this study, Fas receptor and caspase-3 immunoexpression in the optic nerve axons of eyeballs with absolute glaucoma and eyes enucleated following extensive trauma were compared. MATERIAL/METHODS: A series of 25 eyeballs were examined and enucleated during the period of 1994-2005. Seventeen eyeballs were removed from patients with absolute glaucoma who suffered from severe ophthalmalgia and 8 eyeballs were enucleated because of extensive injury on the day of injury or one day thereafter. The samples were obtained from the retrolaminar region of the optic nerve head and evaluated histopathologically. Immunohistochemistry was performed using polyclonal antibodies and the LSAB technique to determine Fas and caspase-3 expression. RESULTS: The percentages of positive Fas receptor and caspase-3 immunohistochemical staining were higher in the axons with absolute glaucoma than in the trauma group (p=0.0084 for Fas, p=0.0322 for caspase-3). CONCLUSIONS: The results indicate that the apoptosis markers Fas receptor and caspase-3 might play a significant role in glaucoma neuropathy at the stage of absolute glaucoma.

[An application of Color Doppler ultrasonography in evaluate of brachytherapy in patients with uveal melanomas]. / Zastosowanie kolorowej ultrasonografii dopplerowskiej do oceny skutecznosci brachyterapii u pacjentów z czerniakiem blony naczyniowej.

UNLABELLED: Uveal melanomas, even those of big size, are recently more readily treated conservatively, with radiotherapy, though the efficiency of this treatment has not been yet established. PURPOSE: Of the study was the assessment of the usefulness of Color Doppler (CD) or Power Doppler (PD) examination in monitoring the effectiveness of brachytherapy in the management of melanomas. MATERIAL AND METHODS: Examination was performed in 15 patients, who were treated because of medium size or large uveal melanomas, with plaque radiation (brachytherapy). CD/PD examination of blood flow within the tumor, with the use of SonoVue contrast agent in several cases, was performed before institution of the therapy and two times after the treatment, as follow-up. RESULTS: Regression of the tumor and gradual atrophy of its neovascularisation was observed in all the examined patients. The enhancement of Color Doppler imaging with contrast agent helps in making decision to further therapeutic options as complex situation. CONCLUSIONS: Color and Power Doppler ultrasonography is a helpful method in monitoring the effectiveness of brachytherapy in patients with uveal melanomas.

[The influence of pregnancy on progression of diabetic retinopathy]. / Wplyw ciazy na progresje retinopatii cukrzycowej.

PURPOSE: Pregnancy is considered an important risk factor of the development and progression of diabetic retinopathy (DR). The aim of the study was to assess whether retinal changes tend to progress during pregnancy in women with type 1 diabetes. MATERIAL AND METHODS: 136 women with type 1 diabetes were enrolled to this 3 years prospective study. The patients were divided according to White's scale into the following classes: B (n=76), C (n=34), D (n=24), R (n=2). Before conception and during pregnancy the patients were treated with intensive insulin therapy to achieve optimal metabolic control. Ophthalmic examination was performed before planned conception, in each trimester of the pregnancy and after delivery. RESULTS: No pathologies were discovered with fundoscopy in all the women belonging to class B, in 22 women from class C and in 4 women from class D. No progression of diabetic retinopathy was observed during the entire period of observation in 12 women from class C and in 20 from class D with nonproliferative DR in the first examination. In 3 women from class C progression of DR were observed in the second trimester with partial improvement after delivery. Visual acuity in these patients also deteriorated. Proliferative DR diagnosed in 2 patients from class R at the beginning of the observation, progressed during the pregnancy to diminish after delivery. CONCLUSIONS: Pregnancy does not influence significantly the progression of pre-existing diabetic retinopathy, provided that proper metabolic control is achieved and patients are subject to systematic ophthalmological control.

[Ocular findings in patients with Steinert myotonic dystrophy]. / Objawy okulistyczne u chorych z dystrofia miotoniczna Steinerta.

The authors present one of many myotonic dystrophies: Steinert myotonic dystrophy (Steinert disease), which is a disease occuring seldom, and causing a lot of problems during the diagnostic and treatment process. Genetic factors, results of the histopathology tests, main clinical symptoms, particularly ophtalmic manifestation are described in this article.

[Biosynthesis of nitric oxide and its function in organism]. / Biosynteza tlenku azotu i jego funkcje w organizmie.

Nitric oxide (NO) is a gas with diverse biological activities produced from L-arginine by nitric oxide synthetase (NOS). This article provides a short overview of the basic function of NO which takes part in smooth muscle relaxation, neurotransmission, modulation of inflammation in a number of tissues and pathological conditions. The discovery of these new physiological and pathological pathways allows for better understanding of many complex processes. It opens a new field for better treatment of many diseases.

[The role of nitric oxide in physiology and pathogenesis of ocular diseases]. / Udzial tlenku azotu w procesach fizjologicznych i patologicznych zachodzacych w oku.

Nitric oxide (NO) is a gas with diverse biological activities produced from arginine by nitric oxide synthetase (NOS). The loss of retinal ganglion cells is a hallmark of many ophthalmic diseases including glaucoma, retinal ischemia due to central artery occlusion and anterior ischemic optic neuropathy. It may well be significant in optic neuritis, optic nerve, trauma and AIDS. NO appears to be involved in the regulation of intraocular pressure, in the modulation of ocular blood flow and in apoptosis. This article gives a short and simplified overview of the biochemistry of NO and its role in physiology and pathogenesis of ocular diseases.

Metalloproteinase 9 and TIMP-1 expression in retina and optic nerve in absolute angle closure glaucoma.

PURPOSE: Glaucoma is one of the most important reason causes of the blindness, associated with retinal ganglion cells (RGC) death. This process is not fully understood, however apoptosis due to hypoxia is one of the most important processes leading to RGC death. Glaucomatous optic neuropathy is characterized by remodeling of the extracellular matrix due to metalloproteinase activation, which leads to loss of RGC and axons at the optic nerve head. The aim of the study was to evaluate metalloproteinase 9 (MMP-9) and tissue metalloproteinase inhibitor-1 (TIMP-1) expression in the retinal ganglion cells and optic nerve axons in 33 eyes with absolute primary glaucoma. MATERIAL/METHODS: To evaluate MMP-9 and TIMP-1 expression primary polyclonal goat antibodies against MMP-9 and TIMP-1 were used. The control group was composed of 8 cases of eyes enucleated and fixed in the first day after trauma. RESULTS: MMP-9 expression was observed in retinal ganglion cells and in the inner nuclear layer of the retina in all the examined cases. In 28 out of 33 glaucomatous eyes, MMP-9 expression was observed in the proliferating glial cells surrounding the optic nerve axons. TIMP-1 expression was observed in 10 out of 33 glaucomatous eyes, only in retinal ganglion cells. None of the examined injured eyes showed MMP-9 and TIMP-1 expression. CONCLUSIONS: MMP-9 activation rather than TIMP-1 may by associated with the pathomechanism of retinal ganglion cell and optic nerve damage in absolute glaucoma.

[Problems of perioperative period in patients with Steinert's myotonic dystrophy operated due to cataract]. / problemy okresu okolooperacyjnego u chorych na dystrofie miotoniczna steinerta, operowanych z powodu zacmy.

Steinert's myotonic dystrophy is a genetically conditioned systemic disease with symptoms related to circulatory, respiratory, muscular, endocrine and mental disturbances. Most if not all of these patients develop lens opacification as a presenting symptom and need to undergo cataract surgery. Nevertheless, selection of a type of anaesthesia can arise to a problem in these patients because local anaesthesia can be insufficient whereas general endotracheal anaesthesia is known, to potentially provoke serious postoperative complications. In this contribution we discuss problems we faced during cataract surgery in three siblings affected by Steinert's myotonic dystrophy. Two of them were operated on in local anaesthesia and developed intraoperative problems related to sudden increase of intraocular pressure, bleeding and vitreous efflux. After receiving a thorough examination the youngest of the three was operated on under short acting general intravenous anaesthesia (propofol and/or benzodiazepines, piperidine derived opioids, non-polarizing paralytics). We conclude that short acting general intravenous anaesthesia can help in avoiding both, local ocular complications during surgery and problems in the postoperative period.

[Genetic abnormalities underlying formation of choroidal melanoma]. / Podloze genetyczne czerniaka zlosliwego blony naczyniowej oka.

Genetic mechanisms underlying formation of ocular and skin melanoma differ in many aspects, the former being still poorly understood. It has been suggested that choroidal melanoma can develop due to accumulation of genetic alterations in the DNA of normal melanocytes. Neoplastic transformation in the choroid can be triggered as a consequence of the following genetic alterations: --deletions and/or amplifications in the genetic material, usually in the chromosome 3, 6, 8, 9, 11, and 18; --point mutations, especially within some egzones, which leads to monosomia or loss of heterozygosity of the chromosome. As a consequence of the above alterations a number of false codons can appear resulting in formation of defective enzymatic proteins. Some of these proteins, like p16 and p14, normally play a role of suppressors of oncogenesis and defects in their structure may result in melanoma formation.

Comparison of ExPress Mini-Device Implantation Alone or Combined with Phacoemulsification for the Treatment of Open-Angle Glaucoma.

We propose comparative assessment of the effectiveness of two surgical methods for the treatment of open-angle glaucoma: (1) ExPress mini-device implantation combined with phacoemulsification and (2) ExPress mini-device implantation alone. In this prospective study, 81 patients (88 phakic eyes) with uncontrolled open-angle glaucoma enrolled for surgery. They were assigned two groups, those with coexisting cataracts (46 eyes; P-ExPress group) and those with glaucoma alone (42 eyes; ExPress group). The follow-up period was 12.9 ± 0.4 months in P-ExPress and 12.2 ± 0.6 months in ExPress group. In both groups the following parameters were measured: best corrected visual acuity (BCVA), intraocular pressure (IOP), number of complications and necessary postoperative interventions, and number of glaucoma medications. The IOP at the end of follow-up was similar in both groups (18.8 ± 5.9 versus 18.1 ± 4.8 mmHg; P = 0.814). There were no statistical differences in the average number of glaucoma medications between ExPress and P-ExPress groups (0.9 ± 1.65 versus 1.3 ± 1.7; P = 0.419) as well as in the number of postoperative complications (26 versus 21%; P = 0.179 in the P-ExPress and ExPress groups, resp.). Both methods are safe and effective for the surgical treatment of open-angle glaucoma. Coexistence of cataracts does not constitute a compelling contraindication for combined surgery.

Prospective Randomized Study Comparing Combined Phaco-ExPress and Phacotrabeculectomy in Open Angle Glaucoma Treatment: 12-Month Follow-Up.

Purpose of the Study. To compare the efficacy and safety of phacotrabeculectomy (P-Trab) and phacoemulsification with the ExPress (P-ExPress) mini glaucoma shunt implantation. Study Plan. Prospective randomized study. Material and Methods. 85 eyes with cataract and unregulated open angle glaucoma. There were 46 eyes in the P-ExPress and 39 the P-Trab group. Intraocular pressure (IOP), the number of antiglaucoma medications, qualified and complete surgical success (defined as IOP ≤ 18.0 mmHg), visual acuity (CDVA), the number of endothelial cells, and postoperative complications and additional procedures were assessed. Results. After 12 months of observation, the average IOP in the P-Express group went from 26.4 ± 9.3 down to 17.1 ± 5 mmHg (P < 0.05) and from 27.9 ± 12.9 down to 15.9 ± 2.7 mmHg in the P-Trab group (P < 0.05). No significant differences in the amount of medications used after surgery and CDVA were discovered between the groups. In the P-ExPress group, greater loss of endothelial cells was noted (CDloss%), compared to the P-Trab group. Conclusions. Both P-ExPress and P-Trab have comparable efficacy and similar early postoperative complication profile. The presence of additional implant (as is the case of the ExPress mini glaucoma shunt implantation) may cause progressive loss of endothelial cells.

Loss of heterozygosity in patients with pseudoexfoliation syndrome.

PURPOSE: The purpose of the study was to evaluate the possible occurrence of loss of heterozygosity (LOH) in the anterior capsule, lens nucleus, iris, and trabeculum samples taken from patients with pseudoexfoliation syndrome (PEX). Loss of heterozygosity in a microsatellite marker locus indicates that the neighboring gene may be inactivated. Previous attempts to find a gene defect that might be responsible for pseudoexfoliation glaucoma have been unsuccessful. METHODS: Specimens of the anterior capsule, the lens nucleus, the iris, the trabeculum, and reference blood samples were collected from 19 PEX patients. Fluorescent multiplex PCR was used to amplify the microsatellite markers located on chromosomes 2, 4, 7, 12, 18, 19, and 21. RESULTS: LOH was found in 58% of the iris specimens and 50% of the anterior capsule specimens collected from PEX patients. The highest incidence of LOH was observed at the marker D7S820. CONCLUSIONS: It is possible, that genetic factors may be involved in the etiology and pathogenesis of PEX.

[The expression of Bcl-2, Bcl-xl, Bak and Bax proteins in axons of the optic nerve in closed-angle glaucoma]. / Ekspresja bialek Bcl-2, Bcl-xl, Bak i Bax w aksonach nerwu wzrokowego u chorych z jaskra dokonana.

PURPOSE: The aim of our study was the evaluation of Bcl-2, Bcl-xl, Bak and Bax immunoexpression in axons of the optic nerve with absolute glaucoma. MATERIAL AND METHODS: This study was conducted on 19 patients with absolute glaucoma, suffered from severe ophthalmalgia, treated of necessity by enucleation in 1991-2003 in our Department of Ophthalmology. The samples were immuno-stained with antibodies for Bcl-2, Bak, Bax and Bcl-xl protein. The reactions were performed in Labelled Streptavidin Avidin Biotin (LSAB) technique. The evaluation of immuno-staining was calculated as the percentage of cells with positive reaction to the total number of cells encountered in 10 representative fields, by light microscopy using a x 20 objective lens. Scores were based on the following scale: (++), over 50% of the field showing positive immuno-staining, (+) 10-50% with positive immunostaining. RESULTS: In our study proapoptotic Bak and Bax protein expression was stronger than antiapoptotic Bcl-2, Bcl-xl protein expression; Bak/Bcl-2 (p = 0.008), Bax/Bcl-2 (p = 0.0007), Bak/Bcl-xl (p = 0.0356), Bax/Bcl-xl (p = 0.0077). CONCLUSIONS: The results of our study demonstrate high proapoptotic trends in axons of the optic nerve in the stage of absolute glaucoma.

[Non-penetrating deep sclerectomy with SK-GEL implant in the patients with pseudoexfoliation glaucoma]. / Gleboka nieperforujaca sklerektomia z wszczepem sródtwardówkowym typu SK-GEL u chorych na jaskre pseudoeksfoliacyjna.

PURPOSE: The aim of this study was to evaluate the effectiveness of non-penetrating deep sclerectomy with SK-GEL implant in the patients with pseudoexfoliation glaucoma. MATERIAL AND METHODS: Non-penetrating deep sclerectomy with SK-GEL implant was performed in 5 eyes of 5 patients aged 65 to 78 (mean age 73 years +/- 5.4). Pseudoexfoliation glaucoma was recognized in all patients. In spite of the intensive pharmacological and laser treatment, sufficient reduction of an intraocular pressure was not obtained. The intraocular pressure before the surgery ranged between 24 and 43.4 mmHg (mean 31 mmHg +/- 7.6). Follow-up period lasted from 36 to 53 days (mean 46 days +/- 7.7). RESULTS: After the surgery, reduction of the intraocular pressure was observed in all subjects. At the moment of discharge from hospital the intraocular pressure ranged from 12 to 26 mmHg (mean 19.6 mmHg +/- 5.12), and at the last control appointment--from 14 to 16 mmHg (mean 14.9 mmHg +/- 0.72). CONCLUSIONS: Non-penetrating deep sclerectomy with SK-GEL implant can be taken into consideration, while planning glaucoma surgery in the patients with pseudoexfoliation syndrome.

[Loss of heterozygosity at microsatellite marker localised near the metalloproteinase gene in patients with PEX syndrome]. / Utrata heterozygotycznosci w markerze mikrosatelitarnym zlokalizowanym w poblizu genu metaloproteinazy u chorych z zespolem pseudoeksfoliacji.

PURPOSE: The aim of the study was to evaluate the possible occurrence of loss of heterozygosity (LOH) at microsatellite marker localised near the area for metalloproteinase gene in the anterior capsule, lens nucleus, iris and trabeculum samples taken from patients with pseudoexfoliation syndrome (PEX). MATERIAL AND METHODS: In our study we examined 19 patients (12 women and 7 men) with PEX syndrome who underwent surgical treatment for glaucoma, cataract or both at the same time. The mean age was 75.5 +/- 4.7, range 64-86. Specimens of the iris, anterior capsule, trabeculum and lens nucleus were taken to evaluate the possible occurrence of LOH at microsatellite marker D7S820 with fluorescent multiplex PCR method. RESULTS: LOH was displayed in 44% specimens of anterior capsule, 33% of iris specimen. In lens nucleus and trabeculum specimen LOH did not occur. CONCLUSIONS: The high frequency of LOH in PEX patients at locus D7S820 suggests that genetic factors may be involved in the etiology and pathogenesis of PEX.

[Morphological parameters of the optic disc in patients with primary open angle glaucoma and low myopia]. / Parametry morfologiczne tarczy nerwu wzrokowego u pacjentów z jaskra pierwotna otwartego kata i krótkowzrocznoscia niskiego stopnia.

PURPOSE: To compare the morphological parameters of the optic disc in patients with low myopia and primary open angle glaucoma (POAG) and in patients with glaucoma without refractive errors. MATERIAL AND METHODS: 53 patients, aged 33-88 (56.2 +/- 11.9) with POAG were qualified for our study. The group was divided into two: first group consisted of 14 patients--11 women and 3 men, aged 41-83 (58.2 +/- 10.9) comprising 28 eye balls with low myopia (-0.5 Dsph to -3.5 Dsph) and POAG. The second group consisted of 38 patients: 24 women and 14 men, aged 33-80 (51.0 +/- 13.4) comprising 71 eye balls including 43 emetropic eyes, 26 eyes with hyperopia (+0.5 Dsph to +3.0 Dsph) and 2 eyes with astigmatism. All patients demonstrated early changes in visual field 1-2 stage due to the Aulhom classification. The measurements of the morphological parameters of the optic disc were made with confocal scanning laser ophthalmoscopy using Heidelberg Retina Tomograph--HRT II with glaucoma software. We analyzed the following parameters: optic disc area, cup area, rim area, cup/disc ratio, linear c/d ratio, mean cup depth, maximum cup depth. The statistical analysis was made using Kolomogarow-Smirnow test. RESULTS: All analyzed parameters were higher in patients with low myopia and POAG than in patients with only POAG. The results in both groups were different but still no statistically significant. CONCLUSIONS: Low myopia has an influence on the optic disc morphology in patients with POAG.