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.

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.

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.

Evaluation of the endothelial cell density and the central corneal thickness in pseudoexfoliation syndrome and pseudoexfoliation glaucoma.

Purpose. Evaluation of central corneal thickness (CCT) and endothelial cell density (ECD) in patients with senile cataract and coexisting pseudoexfoliation (PEX) syndrome with glaucoma (PEXG) and without glaucoma using specular microscopy. Participants and Methods. The study included 122 patients (217 eyes). In this group of patients we identified 133 eyes with PEX syndrome (65 with glaucoma, 68 without glaucoma) and 84 eyes without PEX syndrome. ECD and CCT were measured in each eye by specular microscopy. Results. ECD in eyes with PEX syndrome without glaucoma (2297 ± 359 cell/mm(2)) and in eyes with PEXG (2241 ± 363 cell/mm(2)) was lower than in the control group (2503 ± 262 cell/mm(2)) (P < 0.001). CCT in eyes with PEXG (508.2 ± 32.6 µm) was thinner than in eyes with PEX syndrome without glaucoma (529.7 ± 30.3 µm) and control group (527.7 ± 29.4 µm) (P < 0.001). Conclusions. This research shows that in eyes with PEX syndrome, both with and without glaucoma, ECD was statistically significantly lower than in the control group. In patients with PEXG, CCT was statistically significantly thinner than in the PEX syndrome and control group.

HIF-1 expression in retinal ganglion cells and optic nerve axons in glaucoma.

Glaucoma is a result of increased intraocular pressure leading to damage to retinal ganglion cells and optic nerve axons. The aim of this study was to evaluate HIF-1 expression in optic nerve axons and retinal ganglion cells in 42 eyes enucleated because of complete glaucoma compared to eyes removed because of injury.The immunohistochemical reaction was done and specimens were examined under a light microscope. 57% of cases presented HIF-1 expression in the optic nerve axons, and 52.3% in the retinal ganglion cells. 20 out of 42(47.6%) cases were HIF-1 positive both in the optic nerve axons and in the retinal ganglion cells, and the staining was evident mostly in the nuclear and perinuclear area. Our present results indicate that HIF-1 expression in hypoxic conditions in glaucoma might be a very crucial stage in damage to retinal ganglion cells and optic nerve axons, and might be a successful target for the implementation of neuroprotective drugs.

Loss of heterozygosity (LOH)--implications for human genetic identification.

The aim of this study was assessment of possible effects of loss of heterozygosity on human genetic identification of histolopathogical tissue sections. DNA templates were extracted from tumour tissue specimens excised from oncological patients and from reference blood samples. AmpFlSTR Identifiler PCR Amplification Kit and ABI 310 Genetic Analyzer (Applera) were used to obtain genetic profiles. Frequency of LOH was calculated for respective samples. Fisher's exact test was performed for statistical analysis. Forty-two percent of the 101 cancer cases analysed were found to possess alterations of the microsatellites manifesting with allelic loss. The most frequently altered loci were D3S1358 and D18S51. The alteration was detected in 47% of cases with larynx carcinoma, 44% of cases with uveal melanoma, 60% of cases with cervical cancers, one case of liposarcoma G3 and one case od neurofibrosarcoma. No LOH was found in liposarcoma G1, dermatofibrosarcoma and cystosarcoma protuberans in either primary or recurrent tumours. In benign tumours (lipoma and fibroma) LOH was also absent. During genotyping of DNA extracted from histopathological tissue sections caution should be taken when non-match or exclusion based on few discrepancies is concluded.

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.

[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.

[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.

[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.

[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.

[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.