Automated Quantification of Pathological Fluids in Neovascular Age-Related Macular Degeneration, and Its Repeatability Using Deep Learning.

Purpose: To develop a reliable algorithm for the automated identification, localization, and volume measurement of exudative manifestations in neovascular age-related macular degeneration (nAMD), including intraretinal (IRF), subretinal fluid (SRF), and pigment epithelium detachment (PED), using a deep-learning approach. Methods: One hundred seven spectral domain optical coherence tomography (OCT) cube volumes were extracted from nAMD eyes. Manual annotation of IRF, SRF, and PED was performed. Ninety-two OCT volumes served as training and validation set, and 15 OCT volumes from different patients as test set. The performance of our fluid segmentation method was quantified by means of pixel-wise metrics and volume correlations and compared to other methods. Repeatability was tested on 42 other eyes with five OCT volume scans acquired on the same day. Results: The fully automated algorithm achieved good performance for the detection of IRF, SRF, and PED. The area under the curve for detection, sensitivity, and specificity was 0.97, 0.95, and 0.99, respectively. The correlation coefficients for the fluid volumes were 0.99, 0.99, and 0.91, respectively. The Dice score was 0.73, 0.67, and 0.82, respectively. For the largest volume quartiles the Dice scores were >0.90. Including retinal layer segmentation contributed positively to the performance. The repeatability of volume prediction showed a standard deviations of 4.0 nL, 3.5 nL, and 20.0 nL for IRF, SRF, and PED, respectively. Conclusions: The deep-learning algorithm can simultaneously acquire a high level of performance for the identification and volume measurements of IRF, SRF, and PED in nAMD, providing accurate and repeatable predictions. Including layer segmentation during training and squeeze-excite block in the network architecture were shown to boost the performance. Translational Relevance: Potential applications include measurements of specific fluid compartments with high reproducibility, assistance in treatment decisions, and the diagnostic or scientific evaluation of relevant subgroups.

Molecular Biomarkers of Neovascular Age-Related Macular Degeneration With Incomplete Response to Anti-Vascular Endothelial Growth Factor Treatment.

The standard treatment for neovascular age-related macular degeneration (nAMD) consists of intravitreal anti-vascular endothelial growth factors (VEGF). However, for some patients, even maximal anti-VEGF treatment does not entirely suppress exudative activity. The goal of this study was to identify molecular biomarkers in nAMD with incomplete response to anti-VEGF treatment. Aqueous humor (AH) samples were collected from three groups of patients: 17 patients with nAMD responding incompletely to anti-VEGF (18 eyes), 17 patients affected by nAMD with normal treatment response (21 eyes), and 16 control patients without any retinopathy (16 eyes). Proteomic and multiplex analyses were performed on these samples. Proteomic analyses showed that nAMD patients with incomplete anti-VEGF response displayed an increased inflammatory response, complement activation, cytolysis, protein-lipid complex, and vasculature development pathways. Multiplex analyses revealed a significant increase of soluble vascular cell adhesion molecule-1 (sVCAM-1) [ p = 0.001], interleukin-6 (IL-6) [ p = 0.009], bioactive interleukin-12 (IL-12p40) [ p = 0.03], plasminogen activator inhibitor type 1 (PAI-1) [ p = 0.004], and hepatocyte growth factor (HGF) [ p = 0.004] levels in incomplete responders in comparison to normal responders. Interestingly, the same biomarkers showed a high intercorrelation with r2 values between 0.58 and 0.94. In addition, we confirmed by AlphaLISA the increase of sVCAM-1 [ p < 0.0001] and IL-6 [ p = 0.043] in the incomplete responder group. Incomplete responders in nAMD are associated with activated angiogenic and inflammatory pathways. The residual exudative activity of nAMD despite maximal anti-VEGF treatment may be related to both angiogenic and inflammatory responses requiring specific adjuvant therapy. Data are available via ProteomeXchange with identifier PXD02247.

Initial Clinical Results of the eyeWatch: a New Adjustable Glaucoma Drainage Device Used in Refractory Glaucoma Surgery.

PRéCIS:: In this study, we report clinical results after implantation of an adjustable glaucoma drainage device. The intraocular pressure (IOP) profile was efficiently controlled postoperatively as the resistance to aqueous humor outflow was finely adjusted. PURPOSE: The main purpose of this study was to evaluate the safety and efficacy of the new adjustable glaucoma drainage device eyeWatch used in conjunction with a Baerveldt glaucoma implant in refractory glaucoma. PATIENTS AND METHODS: This was a multicentric, prospective, noncomparative clinical trial. Patients older than 18 years of age suffering from refractory glaucoma after failed surgeries, with IOP of ≥20 mm Hg, in whom a further glaucoma procedure using an aqueous shunt was planned, were enrolled in this study. The primary outcome was the success rate, defined as an IOP≤18 mm Hg and reduction of >20% from baseline, IOP≥6 mm Hg. Secondary outcomes were mean IOP, visual acuity, number of antiglaucoma medications, number, and type of complications. RESULTS: Fifteen patients were included. The mean follow-up time was 15.6±3.5 months. The mean baseline IOP decreased from 26.2±6.8 mm Hg before surgery to 11.9±2.8 mm Hg at 12 months (P<0.001). The mean number of glaucoma medications decreased from 3.0±0.7 before surgery to 0.8±0.9 at last visit (P<0.001). The success rate was 40% for complete success and 93% for overall success at last follow-up. Complication rate was 7%. CONCLUSIONS: The novel glaucoma device allows for perioperative and postoperative noninvasive adjustments of the resistance to aqueous humor outflow. This leads to better management of IOP during the early postoperative period, preventing ocular hypotony and eliminating the need for obstructive elements and reinterventions. The rate of complications was low, IOP was adequately controlled and lowered, with a substantial reduction in the number of antiglaucoma medication.

Prospective Evaluation of XEN Gel Implant in Eyes With Pseudoexfoliative Glaucoma.

PURPOSE: The main purpose of this study was to compare the safety and efficacy of XEN gel implant surgery in patients with pseudoexfoliative glaucoma (PEXG) and primary open-angle glaucoma (POAG). SETTING: This was a prospective, interventional study in a tertiary glaucoma center. METHODS: Fifty-seven eyes (43 patients) with POAG and 53 eyes (42 patients) with PEXG with uncontrolled intraocular pressure (IOP) despite medical treatment underwent combined XEN+cataract surgery or standalone XEN surgery. Mean IOP, mean number of medications at 1-year follow-up, needling rates, and incidence of adverse effects (AEs) were analyzed. Complete success, defined as an IOP <16 mm Hg without medications at 1 year, was also analyzed. RESULTS: Combined XEN+cataract surgery was performed in 72% of POAG and 75% of PEXG eyes (P=0.674), the remainder underwent standalone XEN surgery. Patient characteristics were similar between the 2 groups except for higher age for the PEXG patients (78.5±8.5 vs. 71.3± 8.7 y; P<0.001). Mean medicated IOP was 19.8±5.8 (POAG) and 19.7±8.2 (PEXG) at baseline (P=0.98) and 13.9±4.6 (-29.8%) and 13.6±4.3 mm Hg (-31%) at 1 year (P=0.87), respectively (P<0.01). Mean medications dropped from 1.9±1.6 (POAG) and 2.0±1.3 (PEXG) preoperatively to 0.4±0.8 and 0.5±0.8, respectively at 1 year (P<0.001). A total of 42% (POAG) and 63% (PEXG) eyes achieved complete success (P=0.06) at 1 year. Needling was performed in 36.8% (POAG) versus 37.7% (PEXG) (P=0.923). CONCLUSIONS: The XEN gel implant as a standalone or combined procedure demonstrated similar efficacy and safety results in PEXG and POAG eyes.

Prospective Evaluation of Standalone XEN Gel Implant and Combined Phacoemulsification-XEN Gel Implant Surgery: 1-Year Results.

PURPOSE: To evaluate the safety and efficacy of XEN gel implant (Allergan Inc., Irvine) as a standalone versus combined XEN-Phacoemulsification surgery (XEN+cataract) in glaucoma patients. METHODS: Prospective, interventional study. One-hundred forty-nine eyes (113 patients) with open-angle glaucoma and uncontrolled intraocular pressure (IOP) despite medical treatment were enrolled at a tertiary glaucoma center and followed up for a minimum of 1 year. Approximately two-thirds of patients underwent combined XEN+cataract surgery, while the remainder had XEN alone surgery. Primary outcome was a 20% or more decrease in IOP from medicated baseline at 1 year. Mean IOP, mean number of medications at last follow-up, and incidence of adverse effects were analyzed. RESULTS: Of 149 enrolled eyes, data of 87 (58%) were available at 1 year. A total of 109 (73.2%) eyes underwent XEN+cataract surgery and 40 (26.8%) XEN alone surgery. Mean medicated IOP was 20.0±7.1 at baseline and 13.9±4.3 mm Hg at 1 year (P<0.01), a 31% IOP reduction. Mean medications dropped from 1.9±1.3 preoperatively to 0.5±0.8 at 1 year (P<0.001). In total, 62.1% of patients achieved a ≥20% IOP reduction; this proportion was higher in the XEN alone group. 57.7% of eyes achieved complete success (without any antiglaucoma medications) and 71.1% qualified success (with or without medications) when IOP<16 mm Hg was considered as the definition of success. In all, 37% of patients required needling intervention. Adverse effects included bleb revision in 5 eyes, choroidal detachment in 2 eyes, and second glaucoma surgery in 9 eyes. CONCLUSIONS: The XEN gel implant as a standalone procedure or combined with cataract surgery demonstrated safe and sustained IOP reduction after 1 year.

XEN Gel Implant: a new surgical approach in glaucoma.

INTRODUCTION: Glaucoma is a leading cause of blindness worldwide. Intraocular pressure (IOP) lowering is the only effective treatment strategy. Traditional glaucoma surgeries are generally considered to be unpredictable and associated with a high rate of complications. This has led to the development of a novel XEN Gel Implant, a type of minimally invasive glaucoma surgery (MIGS), lowering the IOP without extensive surgical dissection. AREAS COVERED: A literature search was undertaken on PubMed using the terms XEN glaucoma, gelatin microstent, and MIGS. All the articles and case reports on XEN Gel Implant and selected articles on MIGS were studied and reviewed. We have discussed the results of most studies on XEN Gel Implant related to its efficacy, safety and success. EXPERT COMMENTARY: The XEN Gel Implant effectively lowers IOP and medication use, with a favorable safety profile. Long-term data on its success and cost-effectiveness are lacking. The studies have shown it to be without any serious adverse events and to have good safety profile encouraging future research on this novel implant. There is a need to correctly identify selection criteria for patients, who would benefit the most from the XEN Gel Implant.

Revision of a Leaking Bleb With XEN Gel Stent Replacement.

Minimally invasive glaucoma surgery includes different devices which provide a less invasive and safer means of reducing intraocular pressure. The XEN Gel Stent (Allergan Inc., CA) is an ab interno procedure which creates a subconjunctival drainage pathway. It is a new surgical device and there is a paucity of data on complications and their management. We report a clinical case of a leaking bleb after XEN surgery managed by bleb revision, conjunctival suturing, and XEN replacement.

Corneal-Wavefront guided transepithelial photorefractive keratectomy after corneal collagen cross linking in keratoconus.

PURPOSE: To evaluate the efficacy and safety of Corneal-Wavefront guided transepithelial photorefractive keratectomy (TransPRK) after corneal collagen cross linking (CXL) in keratoconic patients. METHODS: In this retrospective, non-comparative, consecutive case series, 39 keratoconic eyes underwent Corneal-Wavefront guided TransPRK for the correction of aberrations at least 4 months after conventional CXL at SEKAL Rovigo Microsurgery Centre, Rovigo, Italy. Two eyes (5%) underwent a secondary laser retreatment for the improvement of post-operative visual acuity and were not included in this retrospective analysis. The mean age of the patients was 35±12 years (19-64 years) at the time of the surgery. Keratron-Scout (Optikon) topographer was used for diagnostic tests and a flying-spot laser (AMARIS; SCHWIND eye-tech-solutions) was used for the refractive surgery. Complete ophthalmic examinations were performed before and after the surgery (4-36 months postoperatively with a mean follow up time of 10±8 months). RESULTS: Preoperatively, eyes showed irregular astigmatism up to 8D. At last postoperative follow-up, 21 eyes (57%) had UDVA better than 20/40, and six eyes (16%) had UDVA of 20/20. Twenty-three eyes (62%) were within 1.50D of attempted correction in spherical equivalent (mean deviation from target was +1.09±2.36D, range -2.50 to +7.38D). No eye lost 2 Snellen lines of CDVA, and 15 eyes (41%) had an increase of more than 2 lines. CONCLUSIONS: Corneal-Wavefront guided transepithelial PRK ablation profiles after conventional CXL yields to good visual, optical, and refractive results. These treatments are safe and efficacious for the correction of refracto-therapeutic problems in keratoconic patients.

XEN-augmented Baerveldt: A New Surgical Technique for Refractory Glaucoma.

BACKGROUND: Glaucoma drainage devices have traditionally been reserved for patients with refractory glaucoma. However, these devices are prone to various sight-threatening complications. To prevent hypotony after placement of the Baerveldt tube, surgeons traditionally tie the tube with an absorbable suture until encapsulation occurs around the plate. We hypothesized that combining the XEN tube, placing it in the anterior chamber and connecting it to the Baerveldt tube posteriorly, outside the anterior chamber, would minimize 2 main potentially blinding complications: hypotony and corneal disease. PURPOSE: To describe a new surgical technique for refractory glaucoma, combining both the Baerveldt and the XEN tubes in the same surgery. SURGICAL TECHNIQUE: The Baerveldt implant was positioned in the superotemporal quadrant and sutured to the sclera. A scleral flap was executed extending from the anterior margin of the plate for the entire length of the tube to the limbus. The Baerveldt tube was correctly positioned by removing a deeper scleral flap. The XEN tube was then inserted ab externo and inserted into the Baerveldt tube's lumen. The newly formed double tube was then sutured and covered by the first scleral flap and usual suturing of the conjunctiva was performed. CONCLUSIONS: This technique is simple and potentially increases the safety of refractory glaucoma surgeries.

Solar retinopathy: a multimodal analysis.

Purpose. Solar retinopathy is a rare clinical disturbance, for which spectral-domain optical coherence tomography (SD-OCT) findings are not always consistent. We report on two cases of solar retinopathy and discuss its differential diagnosis. Methods. This is an observational case study. Results. A 12-year-old female was referred to ophthalmology for bilateral scotoma. Visual acuity was 20/50 in both eyes. Fundus examination was unremarkable, except for slight yellowish material in the central macula, bilaterally. SD-OCT revealed juxtafoveal microcystic cavities in the outer retina, interruption of the external limiting membrane and the inner and outer segment junctions, with disorganized material in the vitelliform space. Fundus autofluorescence showed hypoautofluorescence surrounded by a relatively hyperautofluorescent ring, bilaterally. Similar clinical and morphological findings were detected in a 27-year-old male. Conclusions. Solar retinopathy has a subtle presentation and patients often deny sun-gazing. SD-OCT and fundus autofluorescence are noninvasive and useful tools for its diagnosis.