A deep learning approach to investigate the filtration bleb functionality after glaucoma surgery: a preliminary study.

PURPOSE: To distinguish functioning from failed filtration blebs (FBs) implementing a deep learning (DL) model on slit-lamp images. METHODS: Retrospective, cross-sectional, multicenter study for development and validation of an artificial intelligence classification algorithm. The dataset consisted of 119 post-trabeculectomy FB images of whom we were aware of the surgical outcome. The ground truth labels were annotated and images splitted into three outcome classes: complete (C) or qualified success (Q), and failure (F). Images were prepared implementing various data cleaning and data transformations techniques. A set of DL models were trained using different ResNet architectures as the backbone. Transfer and ensemble learning were then applied to obtain a final combined model. Accuracy, sensitivity, specificity, area under the ROC curve, and area under the precision-recall curve were calculated to evaluate the final model. Kappa coefficient and P value on the accuracy measure were used to prove the statistical significance level. RESULTS: The DL approach reached good results in unraveling FB functionality. Overall, the model accuracy reached a score of 74%, with a sensitivity of 74% and a specificity of 87%. The area under the ROC curve was 0.8, whereas the area under the precision-recall curve was 0.74. The P value was equal to 0.00307, and the Kappa coefficient was 0.58. CONCLUSIONS: All considered metrics supported that the final DL model was able to discriminate functioning from failed FBs, with good accuracy. This approach could support clinicians in the patients' management after glaucoma surgery in absence of adjunctive clinical data.

Managing the ocular surface after glaucoma filtration surgery: an orphan topic.

BACKGROUND: Ocular surface (OS) disorders before glaucoma filtration surgery (GFS) have been considered to play a crucial role influencing the surgical outcome. Conversely, the impact of surgery itself on the OS is almost completely overlooked, though evidence suggest that ocular surface disease (OSD) may be induced in patients by GFS. This review analyzes the determinants involved in the OSD development after GFS, the clinical features and related consequences, the main diagnostic hallmarks, as well as the therapeutic strategies for its management. METHODS: The PubMed database was utilized for the literature examination. Keywords that were searched included ocular surface disease, glaucoma filtration surgery, filtration bleb, post-surgical management, and quality of life. RESULTS: After GFS, OSD is promoted by peri- and post-operative factors, such as the filtration bleb (FB) development, combined surgical approach with phacoemulsification, the use of antifibrotic agents and the reintroduction of antiglaucoma medications. This particular form of OSD that present similar clinical features to mild to moderate dry eye, can be named as post-glaucoma surgery-OSD (PGS-OSD). PGS-OSD may negatively affect the FB functionality, thus potentially hindering the disease control, and significantly worsen the patient quality of life (QOL). CONCLUSIONS: Clinicians are encouraged to routinely include the OS evaluation after GFS and to consider proper management when the occurrence of PGS-OSD worsen the patient's QOL or exert negative effects to the FB functionality. An outline summarizing the main risk factors and the most appropriate therapeutic options to mitigate the PGS-OSD was proposed to support the routine practice.

Differential Gene and Protein Expression of Conjunctival Bleb Hyperfibrosis in Early Failure of Glaucoma Surgery.

The early failure of glaucoma surgery is mainly caused by over-fibrosis at the subconjunctival space, causing obliteration of the filtration bleb. Because fibrosis has a suspected basis of genetic predisposition, we have undertaken a prospective study to identify upregulated profibrotic genes in a population of glaucoma patients with signs of conjunctival fibrosis and early postoperative surgical failure. Clinical data of re-operated fibrosis patients, hyperfibrosis patients who re-operated more than once in a short time, and control patients with no fibrosis were recorded and analyzed at each follow-up visit. Conjunctival-Tenon surgical specimens were obtained intraoperatively to evaluate the local expression of a panel of genes potentially associated with fibrosis. In order to correlate gene expression signatures with protein levels, we quantified secreted proteins in primary cultures of fibroblasts from patients. Expression of VEGFA, CXCL8, MYC, and CDKN1A was induced in the conjunctiva of hyperfibrosis patients. VEGFA and IL8 protein levels were also increased in fibroblast supernatants. We propose that an increase in these proteins could be useful in detecting conjunctival fibrosis in glaucoma patients undergoing filtering surgery. Molecular markers could be crucial for early detection of patients at high risk of failure of filtration surgery, leading to more optimal and personalized treatments.

A novel surgical technique for the treatment of a filtration bleb extending over 180° after Xen gel stent implantation.

PURPOSE: To describe a novel surgical treatment option for managing a symptomatic filtration bleb extending into the three quadrants with adequate IOP control after Xen gel stent implantation. METHODS: A 62-year-old female with pseudoexfoliative glaucoma with an IOP of 34 mmHg underwent implantation of a Xen to reduce the IOP in her right eye. The IOP responded well to the procedure, but the patient developed a persistent giant filtration bleb with foreign body sensation and pain. A huge filtering bleb of over 180° after Xen implant surgery was managed by splitting the giant bleb into two parts, posterior dissection into the intermuscular space, a biodegradable collagen device implantation, and suturing the conjunctiva in two parts with absorbable and nonabsorbable sutures. RESULTS: Before the operation for treatment of a giant bleb, the patient had an IOP of 12 mmHg, a best-corrected visual acuity (BCVA) of 20/40, corneal dellen, and no antiglaucoma medication. Following the bleb recession procedure, the IOP was 16 mmHg, BCVA improved to 20/20, there were no corneal dellen and the patient reported resolution of her bleb discomfort. The IOP and BCVA remained stable through 18 months of follow-up and no antiglaucoma medications or additional surgical procedures were required. CONCLUSION: The novel technique described here can be one option to treat this rare (over 180°) bleb formation after Xen Gel Stent implantation without adversely affecting IOP control.

Updates on the utility of anterior segment optical coherence tomography in the assessment of filtration blebs after glaucoma surgery.

The formation of filtration blebs is the main drainage mechanism for reducing intraocular pressure after traditional incisional glaucoma surgery such as trabeculectomy and non-penetrating deep sclerotomy. Early and short-lasting blebs may also occur after canaloplasty. Bleb formation also plays an important role after the implantation of glaucoma drainage devices, including Minimally Invasive Glaucoma Surgery devices. Anterior segment optical coherence tomography (AS-OCT) is a rapid and non-invasive high-resolution imaging technique that has evolved in recent years to become a routine examination. Anterior segment optical coherence tomography (AS-OCT) provides key information in the assessment and follow-up of glaucoma surgery, especially in the assessment of filtration blebs. Thus, bleb morphology can be qualitatively classified into diffuse, cystic, encapsulated and flattened, and AS-OCT imaging can also provide several quantitative parameters of the bleb, such as total bleb height, bleb fluid-filled cavity height, bleb wall thickness, number of microcysts and trabeculectomy opening size. These parameters could have an impact on clinical management during follow-up because they may predict the success or failure of the surgery in the early and late postoperative periods. Additionally, they may also guide the procedures used to increase filtration and reduce intraocular pressure, such as bleb needling and laser suture lysis.

[Studying the condition of filtering bleb after glaucoma surgery using optical coherence tomography]. / Opticheskaya kogerentnaya tomografiya v issledovanii sostoyaniya fil'tratsionnoi podushki posle antiglaukomnoi khirurgii.

PURPOSE: To compare the optical coherence tomography (OCT) findings on the condition of filtering bleb (FB) in patients with primary open-angle glaucoma (POAG) who used different local therapy before glaucoma surgery. MATERIAL AND METHODS: The study included a total of 82 patients (82 eyes) followed up after glaucoma surgery: 50 patients (50 eyes) who received preservatives-containing drugs before glaucoma surgery; 32 patients (32 eyes) - who were on preservative-free drug treatment before glaucoma surgery. The examinations were carried out 7 days, 1 and 3 months after micro-invasive sinus trabeculectomy. The condition of filtering bleb was studied using the Visante AS-OCT device, as well as with a slit lamp for clinical observation. Corneal-compensated intraocular pressure (IOPcc) was determined by bi-directional pneumatic applanation of the cornea using the Ocular Response Analyzer (ORA). RESULTS: After 3 months post-op, a functioning FB and intraocular pressure below 15.0 mm Hg were observed in 38 eyes out of 50 (76%) in group 1, in 12 eyes (24%) the FB was nonfuncitonal. In Group 2, 25 eyes out of 32 (78%) had functioning FB and intraocular pressure lower than 15.0 mm Hg; in 7 eyes (22%) the FB was nonfuncitonal. Needling was needed 3 months after the operation in 7 eyes out of 32 (22%) in group 2. The need for needling according to OCT findings in patients of group 1 occurred already one week after surgery for 4 eyes out of 50 (8%), after one month - for 14 eyes (28%). CONCLUSION: In patients on pre-operative drug therapy with preservative-containing medications, the process of scarring in the FB is faster. The OCT method allows early detection of the initial signs of scarring, as well as determining the need for needling.

Expression and filtering of TGF-β2 in aqueous humor and trabecular meshwork of Han and Kazakh patients with PACG / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate the expression level of transforming growth factor β2(TGF-β2)in the aqueous humor and trabecular tissue of patients with primary angle-closure glaucoma(PACG)of Han and Kazakh ethnic groups and the formation of filter bleb after trabeculectomy.<p>METHODS: Prospective research. Between July 2018 to April 2019, 46 PAGG patients(49 eyes)underwent trabeculectomy in our hospital, including 25 Han nationality(26 eyes)and 21 Kazak nationality(23 eyes). Aqueous humor and trabecular tissue were obtained through trabeculectomy. ELISA method was used to detect the content of total aqueous TGF-β2(tTGF-β2)and activated TGF-β2(aTGF-β2). And the expression of TGF-β2 in trabecular tissue was detected by immunohistochemistry and immunofluorescence.<p>RESULTS:Immunohistochemical staining and immunofluorescence staining showed that the expression of TGF-β2 in the trabecular meshwork of Han patients was significantly higher than that of Kazakh patients. ELISA quantitative analysis showed that the aTGF-β2 content of Han and Kazak patients were 172.015±79.367pg/mL and 83.436±41.743pg/mL, respectively, the difference was statistically significant(<i>t</i>=4.794, <i>P</i><0.001). In patients ≥70 years old, the content of tTGF-β2 in the aqueous humor of patients of the two nationalities was 480.124±152.997 and 338.858±72.497pg/mL, respectively, the difference was statistically significant(<i>t</i>=2.421, <i>P</i>=0.026). In the comparison between preoperative and postoperative, there were time differences and interaction effects in intraocular pressure between Han and Kazak patients. At 6mo postoperatively, the formation of type Ⅰ and Ⅱ filter blebs in Han and Kazak patients was different, and the difference was statistically significant(50% <i>vs</i> 78%; χ2=4.841, <i>P</i>=0.028).<p>CONCLUSION: The expression of TGF-β2 in the aqueous humor and trabecular meshwork of patients with PACG in the two ethnic groups is different. The expression of TGF-β2 in the aqueous humor and trabecular meshwork of Kazakh patients is significantly lower, which reduces the promotion of postoperative filtering scar Functional filtration filtration bleb.

Temporary Filtering Bleb Failure Induced by Anterior Chamber Sulfur Hexafluoride Gas: A Complication after Descemet Membrane Endothelial Keratoplasty.

Herein, we report two clinical cases with acute temporary filtering bleb obstruction by gas tamponade after Descemet membrane endothelial keratoplasty (DMEK) surgery and postoperative intraocular pressure (IOP) peaks. Both patients underwent uncomplicated DMEK surgery with 20% sulfur hexafluoride (SF6) anterior chamber tamponade and had previous trabeculectomy for glaucoma. Prior to surgery, both patients showed patent bleb function with low to normal IOP without antiglaucomatous medication. After uneventful DMEK surgery, both patients showed postoperative IOP peaks of up to 50 mm Hg despite patent inferior iridotomy and no sign of a pupillary block. In both cases, SF6 gas bubbles could be visualized obstructing the bleb. Both patients were treated with IOP-lowering agents topically as well as systemically. In addition, anterior chamber paracenteses were performed to reduce the SF6 volume within the anterior chamber. Under this treatment, IOP normalized within the first 18 h after surgery. We hypothesize that the SF6 gas tamponade from the anterior chamber migrates into the ostium and below the bleb, leading to an acute temporary insufficiency of bleb function and to a consecutive IOP peak after surgery. In contrast to a pupillary block, this mechanism cannot be antagonized by preoperative iridotomy and needs to be taken into account for every glaucoma patient with functional bleb undergoing DMEK surgery.

Tear fluid signs associated with filtration blebs, as demonstrated by three-dimensional anterior segment optical coherence tomography.

PURPOSE: To determine the clinical features of tear fluid signs associated with filtration blebs via three-dimensional anterior segment optical coherence tomography (3D AS-OCT). METHODS: In total, 152 eyes (130 patients) with glaucoma that underwent trabeculectomy with mitomycin C were evaluated retrospectively. We investigated tear fluid signs associated with filtration blebs, using 3D AS-OCT with custom software, and compared the findings of lower tear meniscus. We also analyzed postoperative intraocular pressure and the bleb parameters of filtration blebs between eyes with and without tear fluid signs. RESULTS: We found tear fluid signs associated with filtration blebs in 45 (30%) of 152 eyes. The mean postoperative intraocular pressure of the eyes with the tear fluid sign in a filtration bleb was significantly lower than that in eyes without the tear fluid sign (P<0.001). Blebs with tear fluid signs have more frequent identifiable filtration openings, greater total height, increased fluid-filled cavity height, and less wall intensity compared with blebs without these signs. CONCLUSION: We identified tear fluid signs in AS-OCT images on or along filtration blebs that depended on bleb morphology. The occurrence of these signs may be related to the presence of functional blebs, which may thereby control postoperative intraocular pressure.

CSM enhances the filtration bleb survival in rabbit model of experimental glaucoma surgery.

PURPOSE: The aim of this study is to investigate whether CS-g-MMCs conjugate (CSM) could be a new agent to prevent the post-operative fibrosis in a rabbit model of experimental glaucoma filtration surgery. MATERIALS AND METHODS: In a randomized, controlled, masked-observer study, 40 New Zealand White rabbits underwent trabeculectomy in the right eyes and randomly received subconjunctival injection of phosphate buffered saline, chitosan (CS), CSM (100 µg/ml), CSM (200 µg/ml) or Mitomycin C (100 µg/ml). Bleb characteristics and anterior chamber depth were evaluated by slit-lamp examination. The animals were killed on day 14 and 28. Histopathology and immunohistochemistry were performed to determine the amount of the scarring and fibrosis. Ocular toxicity was assessed by histopathology and electron microscope. RESULTS: We found that the five groups were similar with respect to intraocular pressure and anterior chamber depth. The medians for survival days were: 5.5, 8, 17.5, 28 and 16 in the PBS, CS, CSM100, CSM200 and MMC groups, respectively. Both the CSM200 and the MMC group showed a significantly larger bleb area than the CSM100, CS and the PBS group. Less scarring was seen on day 14 and 28 in CSM200 and MMC group than in the PBS, CS and CSM100 group by histology and immunohistochemistry assessment. No damages were found in the rabbit eyes in each group. CONCLUSIONS: Subconjunctival injection of CSM postoperatively can improve the filtration bleb survival in the rabbit model. It can be a safe and effective antimetabolite in glaucoma surgery.

Effects of applying trichostatin A on filtration bleb after filtering surgery in rabbits / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the morphologic changes of of filtration blebs after trichostatin A treatment in an experimental glaucoma filtration surgery ( GFS) . METHODS:Subconjunctival injection TSA, mitomycin C ( MMC) and PBS during the filtering surgery in rabbits. The morphologic changes of filtration blebs were evaluated by Krofeld score method postoperatively days 3, 7, 14, 21, and 28. RESULTS: TSA induced filteation bleds were elevated diffusely within 14d and cystic blebs formed 28d, filtration bleb score was significantly higher in TSA group than that in PBS group. CONCLUSION: TSA can keep the aqueous humor outflow by inhibiting scar formation and prolong the existence of the filtration bleb.

Efficacy of amniotic membrane-assisted bleb revision for elevated intraocular pressure after filtering surgery.

PURPOSE: To compare the effectiveness of standard revision surgery using mitomycin C (MMC) with revision using amniotic membrane transplantation and MMC for elevated intraocular pressure (IOP) after trabeculectomy. PATIENTS AND METHODS: A retrospective, nonrandomized comparative study of 36 eyes of 36 patients with a failed trabeculectomy. Patients were divided into two groups, ie, a nonamnion-transplanted group and an amnion-transplanted group. The amniotic membrane was placed on the scleral flap under the conjunctiva in the amnion-transplanted group. Both groups recovered filtration of aqueous humor from the surgical site with the adjunctive use of MMC. The changes in IOP and cumulative survival rate were compared for the two groups. Success was defined as a 30% reduction in IOP from the preoperative IOP and maintenance below 21 mmHg with or without the use of antiglaucomatous agents. RESULTS: The mean preoperative IOP was not significantly different in the two groups. The mean postoperative IOP in the nonamnion group, 12.1 +/- 5.5 mmHg, was significantly lower than the IOP in the amnion group, 16.0 +/- 3.7 mmHg. Survival curves in the two groups did not reach significantly different levels. CONCLUSIONS: Conventional surgical bleb revision with MMC can significantly reduce the elevated IOP associated with a failed filtration bleb. The use of an amniotic membrane transplant did not improve the surgical outcome in our cases.

Effects of Topical Mitomycin C on Glaucoma Filtration Surgery

We studied the efficacy and safety of using topical mitomycin C(MMC) as an adjunct to glaucoma filtration surgery. Trabeculectomy was performed in 23 eyes of 19 patients with poor surgical prognosis. After the preparation of a scleral flap. 0.2mg or 0.4 mg/ml MMC was applied to the exposed tissue for 5 minutes. The wound was then irrigated with 250ml of normal saline. The follow-up period was from 2 to 12 months(mean 7.8 +/- 4.3 months). Preoperative mean intraocular pressure(IOP) was 33.8 +/- 7.1 mmHg, ranged from 25 to 51 mmHg. The mean IOPs after 1, 3, 6 and 12 months were 10.3 +/- 4.4, 12.5 +/- 6.9, 12.4 +/- 6.6 and 12.3 +/- 6.7 mmHg, respectively. Nineteen(82.6%) among 23 eyes were successfully controlled with the IOP below 20 mmHg without any antiglaucomatous therapies, and success rate was 0.747 by Kaplan-Meier method at Postoperative 12 months. There were early postoperative complications of aqueous leaking from conjunctival wound in 3 eyes(13.0%), shallow anterior chamber in 2 eyes, and hyphema in one eye and one eye had long-term hypotony lasting more than 3 months. Although MMC is simple to use and a potent adjunct to glaucoma filtration surgery, more work will be needed to determine the mechanism of action, indications, dosage and optimal exposure time of MMC.

Effects of topical mitomycin C on glaucoma filtration surgery

We studied the efficacy and safety of using topical mitomycin C (MMC) as an adjunct to glaucoma filtration surgery. Trabeculectomy was performed in 23 eyes of 19 patients with poor surgical prognosis. After the preparation of a scleral flap, 0.2 mg or 0.4 mg/ml MMC was applied to the exposed tissue for 5 minutes. The wound was then irrigated with 250ml of normal saline. The mean follow-up period was 7.8 months. Preoperative mean intraocular pressure (IOP) was 33.8mmHg, and the mean IOPs on 1, 3, 6, and 12 months after operation were 10.3, 12.5, 12.4 and 12.3mmHg, respectively. At postoperative 12 months, 74.7% achieved an IOP of less than or equal to 20mmHg without any antiglaucoma medication. There were early postoperative complications of aqueous leaking from conjunctival wounds in 3 eyes (13.0%), shallow anterior chamber in 2 eyes, and hyphema in one eye and one eye had long-term hypotony lasting more than 3 months. Although MMC is simple to use, it is a potent adjunct to glaucoma filtration surgery, more work should follow to determine the mechanism of action, indications, dosage and optimal exposure time of MMC.

Effects of sodium hyaluronate on filtration bleb in rabbits

Sodium hyaluronate can be used during a trabeculectomy to prevent early postoperative hypotony and shallow anterior chamber. To determine its long-term effect on the outcome of filtration surgery, fifteen rabbits underwent a osterior-lip sclerectomy in both eyes. Into their right eyes 0.2ml sodium hyaluronate, and into left eyes 0.2ml balanced salt solution were injected intracamerally. Gross and histopathological differences of bleb were observed. There was no statistically significant difference in longevity of the filtration bleb.