Continuous Wave Transscleral Cyclophotocoagulation and Endoscopic Cyclophotocoagulation in Childhood Glaucoma: A Meta-analysis.

PURPOSE: To report the outcomes of continuous wave-transscleral cyclophotocoagulation (TS-CPC) and endoscopic cyclophotocoagulation (ECP) in childhood glaucoma. METHODS: We performed a systematic search of relevant databases. We collected data on age, follow-up duration, type of glaucoma, previous surgical interventions, preoperative and postoperative intraocular pressure (IOP), preoperative and postoperative number of glaucoma medications, adverse events, number of sessions, and success rates at different time points. The main outcome measures are the amount of IOP and glaucoma medication reduction. RESULTS: We included 17 studies studying 526 patients (658 eyes); 11 evaluated the effectiveness of TS-CPC (268 patients, 337 eyes), 5 evaluated ECP (159 patients, 197 eyes), and one study compared both techniques (56 patients, 72 eyes for TS-CPC vs. 43 patients, 52 eyes for ECP). The median duration of follow-up was 28 months in the TS-CPC group and 34.4 months in the ECP group. The mean number of treatment sessions was 1.7 in the TS-CPC and 1.3 in the ECP. In the TS-CPC group, the mean IOP was significantly reduced from 31.2±8 to 20.8±8 mmHg at the last follow-up (P<0.001). The mean number of glaucoma medications was reduced from 2.3±1.3 to 2.2±1.3 (P=0.37). In the ECP group, there was also a significant reduction in the mean IOP from 32.9±8 mmHg with a mean of 1.7±0.7 glaucoma medications to 22.6±9.8 mmHg (P<0.0001) on 1.2±1.1 medications (P=0.009) at the last follow-up. CONCLUSION: Both TS-CPC and ECP were effective in reducing the IOP and glaucoma medications in childhood glaucoma. Multiple treatment sessions were required.

An Extensive-Form Game Paradigm for Visual Field Testing via Deep Reinforcement Learning.

Glaucoma is the leading cause of irreversible but preventable blindness worldwide, and visual field testing is an important tool for its diagnosis and monitoring. Testing using standard visual field thresholding procedures is time-consuming, and prolonged test duration leads to patient fatigue and decreased test reliability. Different visual field testing algorithms have been developed to shorten testing time while maintaining accuracy. However, the performance of these algorithms depends heavily on prior knowledge and manually crafted rules that determine the intensity of each light stimulus as well as the termination criteria, which is suboptimal. We leverage deep reinforcement learning to find improved decision strategies for visual field testing. In our proposed algorithms, multiple intelligent agents are employed to interact with the patient in an extensive-form game fashion, with each agent controlling the test on one of the testing locations in the patient's visual field. Through training, each agent learns an optimized policy that determines the intensities of light stimuli and the termination criteria, which minimizes the error in sensitivity estimation and test duration at the same time. In simulation experiments, we compare the performance of our algorithms against baseline visual field testing algorithms and show that our algorithms achieve a better trade-off between estimation accuracy and test duration. By retaining testing accuracy with reduced test duration, our algorithms improve test reliability, clinic efficiency, and patient satisfaction, and translationally affect clinical outcomes.

Neurotrophic Keratopathy After Slow Coagulation Transscleral Cyclophotocoagulation.

PURPOSE: Decreased corneal sensation and subsequent neurotrophic keratopathy (NK) is an uncommon complication after transscleral cyclophotocoagulation (TSCPC). Post-TSCPC NK has been rarely reported in the literature, predominantly after traditional, "pop technique" continuous-wave TSCPC or micropulse CPC. The authors report the first case series of NK after slow-coagulation TSCPC (SC-TSCPC). METHODS: This was a respective chart review of patients who developed NK after SC-TSCPC. The collected data included demographic data, type of glaucoma, risk factors for corneal anesthesia in addition to the number of laser spots, and the extent of the treated area. RESULTS: Four eyes experienced NK after SC-TSCPC. The median time for the development of NK was 4 weeks. At the final visit, 2 patients had a resolution of NK, 1 had a persistent corneal ulcer, and 1 had worsening NK and corneal perforation. CONCLUSIONS: NK is a rare but a vision-threatening complication that can develop after SC-TSCPC in patients with risk factors for decreased corneal sensation. Early diagnosis and proper management are crucial to reducing the risk of vision loss and improving the prognosis of these cases.

Early Experience with the Paul Glaucoma Implant in Childhood Glaucoma: A Case Series.

Purpose: The Paul glaucoma implant (PGI, Advanced Ophthalmic Innovations, Singapore, Republic of Singapore) is a recently developed novel non-valved glaucoma drainage device (GDD) designed to effectively reduce the intraocular pressure (IOP) in glaucoma patients with a theoretically reduced risk of postoperative complications such as hypotony, endothelial cell loss, strabismus, and diplopia. Limited literature has evaluated its use in adult glaucoma; however, its use in pediatric glaucoma has not been reported to date. We present our early experience with PGI in refractory childhood glaucoma. Patients and Methods: This study was retrospective single-surgeon case series in a single tertiary center. Results: Three eyes of 3 patients with childhood glaucoma were enrolled in the study. During nine months of follow-up, postoperative IOP and number of glaucoma medications were significantly lower than preoperative values in all the enrolled patients. None of the patients developed postoperative complications including postoperative hypotony, choroidal detachment, endophthalmitis, or corneal decompensation. Conclusion: PGI is an efficient and relatively safe surgical treatment option in patients with refractory childhood glaucoma. Further studies with larger number of participants and longer follow-up period are required to confirm our encouraging results.

Clinical Factors Impacting Outcomes From Failed Trabeculectomy Leading to Glaucoma Drainage Device Implantation and Subsequent Penetrating Keratoplasty.

PRCIS: We evaluated the factors that impacted time from glaucoma drainage implant (GDI) surgery to penetrating keratoplasty (PK) in eyes with previously clear corneas (ie, GDI-first sequence), and that specifically underwent a trabeculectomy before GDI surgery for intraocular pressure (IOP) control. PURPOSE: To describe through an event-triggered data collection method the clinical course and the long-term outcomes of 2 procedures that are commonly performed sequentially in complex clinical situations: GDI surgery and PK. The study investigates the clinical factors associated with the progression to PK and determines the GDI success rate and graft survival. METHODS: A single, tertiary-care center retrospective interventional cases series including patients with a sequential history of trabeculectomy, GDI surgery, and PK from 1999 to 2009. Outcome measures included IOP, visual acuity, graft failure, GDI failure, and time from GDI to PK. RESULTS: Of the eyes, 56% had primary open angle glaucoma. The time from the last trabeculectomy to GDI was 66.5 ± 66.7 months. Of the eyes, 84% received a Baerveldt GDI. Time from GDI to PK was 36.4 ± 28.4 months. IOP at the time of PK was between 5 mm Hg and 21 mm Hg in 90% of eyes. At the last follow-up, 48% of grafts were clear. At 5 years post-PK, 33% of corneal grafts remained clear, whereas 81% of tubes remained functional. CONCLUSIONS: Nearly half of the corneal grafts are clear at the last long-term follow-up. Graft failure occurs at a higher rate than tube failure suggesting that IOP control is only one and possibly not the most important factor in graft survival in eyes with prior glaucoma surgery.

Slow-Coagulation Transscleral Cyclophotocoagulation Laser Treatment for Medically Uncontrolled Secondary Aphakic Adult Glaucoma.

PRCIS: Slow-coagulation CW-TSCPC is an efficacious, relatively safe, and non-incisional laser treatment option as an initial surgical glaucoma management choice, in secondary aphakic adult glaucoma that is medically uncontrolled. PURPOSE: This study evaluates the outcomes of slow-coagulation continuous wave transscleral cyclophotocoagulation (CW-TSCPC) laser for treating secondary aphakic adult glaucoma after complicated cataract surgery as a primary surgical intervention. MATERIALS AND METHODS: A retrospective chart review of adult aphakic eyes with medically uncontrolled glaucoma underwent slow-coagulation CW-TSCPC as a primary surgical glaucoma intervention was performed. Surgical success was the primary outcome measure. Success was defined as postoperative intraocular pressure (IOP) between 6 and 21 mm Hg with ≥20% reduction compared with baseline and no need for further glaucoma surgeries or development of vision-threatening complications. The secondary outcomes included changes in IOP, glaucoma medication numbers, visual acuity, and postoperative complications during the first year after laser treatment after laser treatment. RESULTS: This study included 41 eyes of 41 patients. The mean age of study participants was 66.7±13.1 years, with a mean follow-up duration of 19±3.5 months. At one year, the success rate was 63.4%. A statistically significant reduction of the IOP was observed, with the mean IOP decreasing from 29.6±5.8 mm Hg with a mean of 3.9±1.0 medications at baseline to a mean of 19.0±6.4 mm Hg with a mean of 2.5±1.2 medications at 12 months ( P <0.001). Four eyes received CW-TSCPC retreatment, and 2 eyes required incisional glaucoma surgeries. Reported postoperative complications included: visual acuity decline ≥2 lines in 7 eyes, iritis in 6 eyes, hyphema in 5 eyes, cystoid macular edema in 2 eyes, and transient hypotony in 1 eye. CONCLUSION: Slow-coagulation CW-TSCPC is an efficacious, relatively safe, and non-incisional laser treatment option as an initial surgical glaucoma management choice, in secondary aphakic adult glaucoma that is medically uncontrolled.

RGC-Net: An Automatic Reconstruction and Quantification Algorithm for Retinal Ganglion Cells Based on Deep Learning.

Purpose: The purpose of this study was to develop a deep learning-based fully automated reconstruction and quantification algorithm which automatically delineates the neurites and somas of retinal ganglion cells (RGCs). Methods: We trained a deep learning-based multi-task image segmentation model, RGC-Net, that automatically segments the neurites and somas in RGC images. A total of 166 RGC scans with manual annotations from human experts were used to develop this model, whereas 132 scans were used for training, and the remaining 34 scans were reserved as testing data. Post-processing techniques removed speckles or dead cells in soma segmentation results to further improve the robustness of the model. Quantification analyses were also conducted to compare five different metrics obtained by our automated algorithm and manual annotations. Results: Quantitatively, our segmentation model achieves average foreground accuracy, background accuracy, overall accuracy, and dice similarity coefficient of 0.692, 0.999, 0.997, and 0.691 for the neurite segmentation task, and 0.865, 0.999, 0.997, and 0.850 for the soma segmentation task, respectively. Conclusions: The experimental results demonstrate that RGC-Net can accurately and reliably reconstruct neurites and somas in RGC images. We also demonstrate our algorithm is comparable to human manually curated annotations in quantification analyses. Translational Relevance: Our deep learning model provides a new tool that can trace and analyze the RGC neurites and somas efficiently and faster than manual analysis.

Cost analysis of childhood glaucoma surgeries using the US Medicaire allowable costs.

AIM: To analyze and calculate the relative cost of various childhood glaucoma surgical interventions per mm Hg intraocular pressure (IOP) reduction ($/mm Hg). METHODS: Representative index studies were reviewed to quantitate the reduction of mean IOP and glaucoma medications for each surgical intervention in childhood glaucoma. A US perspective was adopted, using Medicare allowable costs to calculate cost/mm Hg IOP reduction ($/mm Hg) at 1y postoperatively. RESULTS: At 1y postoperatively, the cost/mm Hg IOP reduction was $226/mm Hg for microcatheter-assisted circumferential trabeculotomy, $284/mm Hg for cyclophotocoagulation, $288/mm Hg for conventional ab-externo trabeculotomy, $338/mm Hg for Ahmed glaucoma valve, $350/mm Hg for Baerveldt glaucoma implant, $351/mm Hg for goniotomy, and $400/mm Hg for trabeculectomy. CONCLUSION: Microcatheter-assisted circumferential trabeculotomy is the most cost-efficient surgical method to lower IOP in childhood glaucoma, while trabeculectomy is the least cost-efficient surgical method.

The role of monocytes in optic nerve injury.

Monocytes, including monocyte-derived macrophages and resident microglia, mediate many phases of optic nerve injury pathogenesis. Resident microglia respond first, followed by infiltrating macrophages which regulate neuronal inflammation, cell proliferation and differentiation, scar formation and tissue remodeling following optic nerve injury. However, microglia and macrophages have distinct functions which can be either beneficial or detrimental to the optic nerve depending on the spatial context and temporal sequence of their activity. These divergent effects are attributed to pro- and anti-inflammatory cytokines expressed by monocytes, crosstalk between monocyte and glial cells and even microglia-macrophage communication. In this review, we describe the dynamics and functions of microglia and macrophages in neuronal inflammation and regeneration following optic nerve injury, and their possible role as therapeutic targets for axonal regeneration.

Expanding the mutational spectrum of FHONDA syndrome.

AIM: The aim of the study is to present a rare case of Foveal Hypoplasia, Optic Nerve Decussation defects, and Anterior segment dysgenesis (FHONDA) confirmed by genetic testing with two separate pathogenic mutations in the SLC38A8 gene. MATERIALS AND METHODS: This was a case report. RESULTS: A 3-month-old female presented to a neuro-ophthalmology clinic with nystagmus. Her past medical and family history was unremarkable. Her examination demonstrated horizontal pendular nystagmus and small optic nerves with foveal hypoplasia bilaterally. Neuroimaging was unremarkable. She underwent an examination under anesthesia and electroretinogram (ERG). Her anterior segment examination was normal, and dilated fundus examination demonstrated foveal hypoplasia with diffuse pigment granularity. The ERG was normal. Genetic testing revealed two mutations in the SLC38A8 gene, p.Glu233Lys:c.697 G>A (pathogenic) and p.Asp283Ala:c.848A>C (likely pathogenic) with positive parental segregation analysis. Therefore, she was diagnosed with FHONDA. CONCLUSIONS: To our knowledge, this is the first report of a patient with FHONDA who is compound heterozygous for these two SLC38A8 mutations, which represents an expansion of the known mutational spectrum associated with this syndrome. Moreover, it may provide guidance into genetic counseling for patients and parents with these mutations.

Outcomes of primary surgical treatment of medically recalcitrant post-keratoplasty glaucoma with transscleral cyclophotocoagulation.

PURPOSE: To report the outcomes of slow-coagulation continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) in post-keratoplasty glaucoma refractory to medical therapy. METHODS: Medical records of 47 patients (mean age of 70.7 ± 15.7 years and follow-up of 13.9 ± 7.1 months) were retrospectively enrolled. All patients had the diagnosis of secondary glaucoma after penetrating keratoplasty (PKP; n = 28) or Descemet's stripping automated endothelial keratoplasty (DSAEK; n = 19) with no previous history of incisional glaucoma or TSCPC surgeries. Study participants underwent slow-coagulation CW-TSCPC (1250-milliwatt power and 4-second duration). RESULTS: A statically significant reduction of IOP from 31.8 ± 8.0 mmHg preoperatively to 16.9 ± 9.0 mmHg postoperatively was noted (p < 0.001). Similarly, the number of glaucoma medications decreased from 4.0 ± 1.0 to 2.7 ± 1.4 (p < 0.001). The overall success rates at 12 and 24 months were 68.1% and 66.0%, respectively, with no difference in success rates between post-PKP and post-DSAEK subgroups (p = 0.836). No significant changes in VA or central corneal thickness (CCT) were observed (p = 0.345 and 0.311, respectively). One (3.3%) patient had a graft rejection. The majority of the complications noted during this study were mild and transient. CONCLUSIONS: Our study suggests that slow-coagulation TSCPC may be a safe and efficient surgical glaucoma treatment modality in patients with medically uncontrolled post-keratoplasty glaucoma.

New glaucoma drainage implants available to glaucoma surgeons.

PURPOSE OF REVIEW: Glaucoma drainage device (GDD) implantation surgery is commonly performed by glaucoma specialists to treat complex and refractory glaucomas. Relative safety and efficacy data from randomized controlled trials conducted in the last two decades have sparked the interest in GDDs as possible surgical options earlier in the course of the disease than has traditionally been practiced. However, until recently, advances in the design and techniques of GDD surgery have fallen short of this increasing interest. RECENT FINDINGS: Most recently, new GDDs that possess novel design features have become available to glaucoma specialists. Two of these new devices are the Ahmed ClearPath and the Paul glaucoma implant. These devices have demonstrated promising outcomes that are comparable to those of traditional implants. Additionally, given their unique respective features, these devices may streamline surgical technique due to ease of insertion and afford better safety and efficacy outcomes in certain patients. SUMMARY: The recent introduction of new GDDs has been long awaited by glaucoma surgeons. Although early results are promising, long-term data and comparison of outcomes to those of traditional filtering surgery and commonly implanted devices are needed before these devices can be the new standard of care in glaucoma tube shunt surgery.

Primary slow-coagulation transscleral cyclophotocoagulation laser treatment for medically recalcitrant neovascular glaucoma.

AIMS: To report treatment outcomes of slow-coagulation continuous-wave transscleral cyclophotocoagulation (TSCPC) as an initial surgical intervention in patients with neovascular glaucoma (NVG). METHODS: A retrospective study including 53 patients (mean age of 69.6±16.6 years and mean follow-up of 12.7±8.9 months) with a diagnosis of NVG and no previous incisional glaucoma or cyclophotocoagulation surgeries. All patients underwent slow-coagulation continuous-wave TSCPC (1250-milliwatt power and 4-second duration).Primary outcome measure was surgical success defined as an intraocular pressure (IOP) from 6 to 21 mm Hg with a reduction ≥20% from baseline, no reoperation for glaucoma and no loss of light perception vision. Secondary outcome measures include IOP, glaucoma medications, visual acuity (VA) and complications. RESULTS: IOP decreased from 40.7±8.6 mm Hg preoperatively to 18.4±12.2 mm Hg postoperatively (p<0.001). The preoperative number of glaucoma medications dropped from 3.3±1.1 at baseline to 2.0±1.5 at the last postoperative visit (p<0.001). The cumulative probabilities of success at 12 and 24 months were 71.7% and 64.2 %, respectively. Mean logarithm of the minimum angle of resolution VA was relatively unchanged from 2.27±0.63 to 2.25±0.66 at the last follow-up visit (p=0.618). The most common observed complications were decrease in baseline VA (13.2%) and anterior chamber inflammation (9.4%). CONCLUSIONS: Slow-coagulation TSCPC is an effective and relatively safe initial surgical intervention in medically uncontrolled NVG.

Hematogenous Macrophages Contribute to Fibrotic Scar Formation After Optic Nerve Crush.

Although glial scar formation has been extensively studied after optic nerve injury, the existence and characteristics of traumatic optic nerve fibrotic scar formation have not been previously characterized. Recent evidence suggests infiltrating macrophages are involved in pathological processes after optic nerve crush (ONC), but their role in fibrotic scar formation is unknown. Using wild-type and transgenic mouse models with optic nerve crush injury, we show that macrophages infiltrate and associate with fibroblasts in the traumatic optic nerve lesion fibrotic scar. We dissected the role of hematogenous and resident macrophages, labeled with Dil liposomes intravenously administered, and observed that hematogenous macrophages (Dil+ cells) specifically accumulate in the center of traumatic fibrotic scar while Iba-1+ cells reside predominantly at the margins of optic nerve fibrotic scar. Depletion of hematogenous macrophages results in reduced fibroblast density and decreased extracellular matrix deposition within the fibrotic scar area following ONC. However, retinal ganglion cell degeneration and function loss after optic nerve crush remain unaffected after hematogenous macrophage depletion. We present new and previously not characterized evidence that hematogenous macrophages are selectively recruited into the fibrotic core of the optic nerve crush site and critical for this fibrotic scar formation.

A Novel Cost-Effective Simulation Model for Continuous Curvilinear Capsulorhexis.

Introduction: We describe and validate a low-cost simulation model for practicing anterior lens capsule continuous curvilinear capsulorhexis (CCC). Methods: A simulation model for CCC was developed from widely available low-cost materials. Ophthalmologists attending the annual scientific meeting of the Research Institute of Ophthalmology, Giza, Egypt, were asked to perform a five CCC model task and then anonymously answer a questionnaire that assessed the realism and training utility of the model using a five-point Likert scale (1 = unacceptable, 2 = poor, 3 = acceptable, 4 = favorable and 5 = excellent). Results: Twenty-seven ophthalmologists completed the task and the anonymous questionnaire. Overall, participants felt that the model simulated CCC step in cataract surgery well (mean: 3.5) and was comparable to other kinds of CCC simulation models (mean: 3.3). The model scored highly for its overall educational value (mean: 4.00) and for enlarging a small CCC (mean:3.7), while the feasibility of this model in practicing the management of a runaway leading edge of CCC scored 2.9. Conclusion: This model may provide an alternative method for training for CCC and other anterior lens capsule-related maneuvers. This option may be particularly helpful for residency training programs with limited access to virtual reality simulators or commercially available synthetic eye models.