Monogenic gene therapy for glaucoma and optic nerve injury

The prevalence of glaucoma, the second leading cause of global blindness, is increasing due to aging populations. In glaucoma, degeneration of the optic nerve and retinal ganglion cells(RGCs) causes visual field defects and eventual blindness.

p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model

Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

Glaucoma surgery experiments using digital microscope-integrated optical coherence tomography and OCT-compatible instruments

There is a certain failure rate in traditional glaucoma surgery because of the lack of depth information in microscope images.In this work,we present a digital microscope-integrated optical coherence tomography(MIOCT)system and several custom-made OCT-compatible instruments for glaucoma surgery.Sixteen ophthalmologists were asked to perform trabeculectomy and canaloplasty on live porcine eyes using the system and instruments.After surgery,a subjective feedback survey about the user experience was taken.The experiment results showed that our system can help surgeons easily locate important tissue structures during surgery.The custom-made instruments also solved the shadowing problem in OCT imaging.Surgeons preferred to use the system in their future practice.

Uveitis glaucoma hyphema syndrome as a result of glaucoma implant: A case report

BACKGROUND Glaucoma is caused by increased intraocular pressure(IOP)that damages the optic nerve,leading to blindness.The Ahmed glaucoma valve(AGV)is a glau-coma drainage implant device that is used in glaucoma patients with uncontrolled IOP.A possible complication after any ocular surgery however is hyphema,which can itself progress to uveitis glaucoma hyphema(UGH)syndrome on rare occasions.UGH syndrome has not yet been reported as a complication of AGV implantation.CASE SUMMARY Here,we have reported a case of a 55-year-old female who developed both hyphema and pigmentation as a result of AGV implantation.We confirmed UGH syndrome secondary to AGV implantation after the patient underwent another surgery to shorten and reposition the AGV tube.After the second surgery,the patient’s IOP was reduced,and she had a clear cornea and no signs of hyphema.CONCLUSION This first report of UGH syndrome as a complication of AGV implantation reminds clinicians that frequent follow-up is paramount.

Patient satisfaction and follow-up adherence to glaucoma case management clinic in China

AIM:To assess glaucoma patient satisfaction and follow-up adherence in case management and identify associated predictors to improve healthcare quality and patient outcomes.METHODS:In this cross-sectional study,a total of 119 patients completed a Patient Satisfaction Questionnaire-18 and a sociodemographic questionnaire.Clinical data was obtained from the case management system.Follow-up adherence was defined as completing each follow-up within±30d of the scheduled time set by ophthalmologists during the study period.RESULTS:Average satisfaction scored 78.65±7,with an average of 4.39±0.58 across the seven dimensions.Age negatively correlated with satisfaction(P=0.008),whilst patients with follow-up duration of 2 or more years reported higher satisfaction(P=0.045).Multivariate logistics regression analysis revealed that longer follow-up durations were associated with lower follow-up adherence(OR=0.97,95%CI,0.95-1.00,P=0.044).Additionally,patients with suspected glaucoma(OR=2.72,95%CI,1.03-7.20,P=0.044)and those with an annual income over 100000 Chinese yuan demonstrated higher adherence(OR=5.57,95%CI,1.00-30.89,P=0.049).CONCLUSION:The case management model proves effective for glaucoma patients,with positive adherence rates.The implementation of this model can be optimized in the future based on the identified factors and extended to glaucoma patients in more hospitals.

Morphological disruption and visual tuning alterations in the primary visual cortex in glaucoma(DBA/2J)mice

Glaucoma is a leading cause of irreve rsible blindness wo rldwide,and previous studies have shown that,in addition to affecting the eyes,it also causes abnormalities in the brain.However,it is not yet clear how the primary visual cortex(V1)is altered in glaucoma.This study used DBA/2J mice as a model for spontaneous secondary glaucoma.The aim of the study was to compare the electrophysiological and histomorphological chara cteristics of neurons in the V1between 9-month-old DBA/2J mice and age-matched C57BL/6J mice.We conducted single-unit recordings in the V1 of light-anesthetized mice to measure the visually induced responses,including single-unit spiking and gamma band oscillations.The morphology of layerⅡ/Ⅲneurons was determined by neuronal nuclear antigen staining and Nissl staining of brain tissue sections.Eighty-seven neurons from eight DBA/2J mice and eighty-one neurons from eight C57BL/6J mice were examined.Compared with the C57BL/6J group,V1 neurons in the DBA/2J group exhibited weaker visual tuning and impaired spatial summation.Moreove r,fewer neuro ns were observed in the V1 of DBA/2J mice compared with C57BL/6J mice.These findings suggest that DBA/2J mice have fewer neurons in the VI compared with C57BL/6J mice,and that these neurons have impaired visual tuning.Our findings provide a better understanding of the pathological changes that occur in V1 neuron function and morphology in the DBA/2J mouse model.This study might offer some innovative perspectives regarding the treatment of glaucoma.

Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective noncomparative study

AIM:To report a one-year clinical outcomes of low-dose laser cycloplasty(LCP)among malignant glaucoma patients.METHODS:In this prospective,multicenter,noncomparative clinical study,participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in China.Patients were followed up at 1wk,1,3,6,and 12mo.Intraocular pressure(IOP),number of glaucoma medications,anterior chamber depth(ACD),and complications were recorded.Anatomical success was defined as the reformation of the anterior chamber based on slit-lamp biomicroscopy.Recurrence was defined by the presence of a shallow orflat anterior chamber after initial recovery from treatment.RESULTS:A total of 34 eyes received LCP.Mean IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg(P<0.001)with 2.9±1.6 medications(P=0.046)at 1d,and 17.4±6.7 mm Hg(P<0.001)with 1.3±1.7 medications(P<0.001)at 12mo.The ACD increased from 1.1±0.8 mm at baseline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo,respectively.A total of 32(94.1%)eyes achieved initial anatomical success.During follow-up,2(5.9%)eyes failed and 8(23.5%)eyes relapsed,yielding a 12-month anatomical success rate of 64.3%.Complications including anterior synechia(8.82%),choroidal/ciliary detachment(5.88%)and hypopyon(2.94%)were observed within 1wk.CONCLUSION:LCP is simple,safe,and effective in reforming the anterior chamber in malignant glaucoma.

Navigating the intersection of psychiatry and ophthalmology:A comprehensive review of depression and anxiety management in glaucoma patients

Glaucoma,a prevalent and debilitating eye disease,has long been associated with vision impairment and blindness.However,recent research has shed light on the often-underestimated psychological dimensions of this condition.Anxiety and depression,two pervasive psychiatric comorbidities,have been increasingly recognized among glaucoma patients.This comprehensive review aims to explore the intricate relationship between psychiatry and ophthalmology,in the context of managing depression and anxiety in glaucoma patients.By meticulously examining peer-reviewed literature,we synthesize current knowledge on the prevalence,risk factors,and underlying mechanisms of anxiety and depression in glaucoma.The evidence reveals that glaucoma patients face an elevated risk of experiencing these mood disorders.Factors such as progressive vision loss,complex medication regimens,and the fear of further visual deterioration contribute to their vulnerability.Moreover,we delve into the bidirectional relationship between glaucoma and mood disorders,shedding light on the complex interplay between ocular and emotional health.Our review investigates the implications of anxiety and depression on glaucoma management,including their potential impact on treatment adherence,disease progression,and overall quality of life.We also explore the neurobiological pathways linking glaucoma and mood disorders,providing a foundation for future research and potential therapeutic interventions.In conclusion,recognizing the psychological burden carried by glaucoma patients is essential for holistic and patient-centered care.This review underscores the pressing need for integrated approaches that bring together ophthalmological and psychiatric expertise to optimize the well-being of individuals facing the challenges of glaucoma.By addressing anxiety and depression in glaucoma care,healthcare providers can enhance the overall quality of life for these patients,ultimately leading to improved outcomes and a brighter future for those affected by this condition.This review offers valuable insight for healthcare practitioners and researchers,providing a concise overview of key topics and research in the field of managing depression and anxiety in glaucoma patients.

Unveiling the silent link:Normal-tension glaucoma's enigmatic bond with cardiac blood flow

This comprehensive review embarks on a captivating journey into the complex relationship between cardiology and normal-tension glaucoma(NTG),a condition that continues to baffle clinicians and researchers alike.NTG,characterized by optic nerve damage and visual field loss despite normal intraocular pressure,has long puzzled clinicians.One emerging perspective suggests that alterations in ocular blood flow,particularly within the optic nerve head,may play a pivotal role in its pathogenesis.While NTG shares commonalities with its high-tension counterpart,its unique pathogenesis and potential ties to cardiovascular health make it a fascinating subject of exploration.It navigates through the complex web of vascular dysregulation,blood pressure and perfusion pressure,neurovascular coupling,and oxidative stress,seeking to uncover the hidden threads that tie the heart and eyes together in NTG.This review explores into the intricate mechanisms connecting cardiovascular factors to NTG,shedding light on how cardiac dynamics can influence ocular health,particularly in cases where intraocular pressure remains within the normal range.NTG's enigmatic nature,often characterized by seemingly contradictory risk factors and clinical profiles,underscores the need for a holistic approach to patient care.Drawing parallels to cardiac health,we examine into the shared vascular terrain connecting the heart and the eyes.Cardiovascular factors,including systemic blood flow,endothelial dysfunction,and microcirculatory anomalies,may exert a profound influence on ocular perfusion,impacting the delicate balance within the optic nerve head.By elucidating the subtle clues and potential associations between cardiology and NTG,this review invites clinicians to consider a broader perspective in their evaluation and management of this elusive condition.As the understanding of these connections evolves,so too may the prospects for early diagnosis and tailored interventions,ultimately enhancing the quality of life for those living with NTG.

Suicide risk in juvenile open angle glaucoma patients

AIM:To investigate the association between juvenile open angle glaucoma(JOAG)and mental health among Koreans.METHODS:This study used nationally representative data from the 8th Korea National Health and Nutrition Examination Survey(KNHANES)2021.Glaucoma diagnosis followed the International Society of Geographical and Epidemiological Ophthalmology criteria based on glaucomatous structural defects,visual field defects,corrected vision,and intraocular pressure.As outcomes,suicidal behaviors,psychiatric counseling,and depression were evaluated through mental health questionnaires.Odds ratios(ORs)with 95%confidence intervals(CIs)were estimated using logistic regression models,adjusting for covariates.RESULTS:Among 7090 participants,3446 met the inclusion criteria for analysis,and 88(2.6%)were diagnosed with open angle glaucoma(OAG).After adjusting for age,sex,and best-corrected visual acuity(VA),participants with OAG were revealed to have significantly higher odds of suicidal behaviors(i.e.,ideation,planning,or attempts)compared with those without OAG(OR:2.70;95%CI:1.12-6.54;P=0.028).This association remained significant after further adjustments for socioeconomic status,lifestyle factors,and presence of chronic conditions(P=0.031 and 0.035,respectively).However,there was no significant difference for the other two outcomes,psychiatric counseling and depression.An age-stratified analysis revealed a stronger association between OAG and suicidal behaviors in younger JOAG participants(<40y)than in older OAG participants(≥40y;OR:3.80 vs 2.22;95%CI:0.79-18.22 vs 0.56-8.80,respectively).CONCLUSION:OAG patients show a higher risk of suicidal behaviors than those without glaucoma particularly in JOAG patients.

Glycolysis and glucose metabolism as a target for bioenergetic and neuronal protection in glaucoma

Vision is arguably our most valued sense,yet approximately 340 million people globally suffer blindness or moderate visual impairment,highlighting the need to further develop and advance treatments for ophthalmic diseases.Glaucoma refers to a group of ocular disorders united by a clinically characteristic optic neuropathy with associated retinal ganglion cell loss.

Glaucoma drainage device implantation and cyclophotocoagulation in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty

AIM:To compare the surgical outcomes of glaucoma drainage device implantation(GDI)and trans-scleral neodymium:YAG cyclophotocoagulation(CPC)in the management of refractory glaucoma after Descemetstripping automated endothelial keratoplasty(DSAEK).METHODS:This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery(15 with GDI and 14 with CPC).The main outcome measures were intraocular pressure(IOP),glaucoma surgery success rate(defined as IOP of 6–21 mm Hg without additional anti-glaucoma operation),number of glaucoma medications,endothelial graft status,and best-corrected visual acuity(BCVA).RESULTS:The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries,both for the GDI and CPC groups.Both groups showed significant IOP reduction after glaucoma surgery.The GDI group presented a significantly higher success rate in IOP control than the CPC group(60%vs 21.4%,P=0.03).Both procedures significantly decreased the number of glaucoma medications(P=0.03).Forty percent and 57%of cases in the GDI and the CPC group,respectively,experienced endothelial graft failure during follow-up(P=0.36).Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group.CONCLUSION:Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK.GDI is preferable to CPC in refractory glaucoma cases after DSAEK,as it manifests a significantly higher success rate for IOP control,similar endothelial graft failure rate,and relatively preserves BCVA than CPC.

Two become one:combination of two risk factors in a new glaucoma animal model

Glaucoma is a group of eye diseases characterized by progressive loss of retinal ganglion cells(RGCs)and optic nerve degeneration.During this process,the visual field is reduced,and blindness may ultimately occur.Worldwide,glaucoma is the second leading cause of blindness,with about 80 million people affected.Glaucoma is a multifactorial disease and due to its complexity,the exact pathomechanisms are not fully understood yet.However,different risk factors,such as elevated intraocular pressure(IOP),age,or myopia,have been identified to date(EGS,2021).

An Improved Deep Learning Framework for Automated Optic Disc Localization and Glaucoma Detection

Glaucoma disease causes irreversible damage to the optical nerve and it has the potential to cause permanent loss of vision.Glaucoma ranks as the second most prevalent cause of permanent blindness.Traditional glaucoma diagnosis requires a highly experienced specialist,costly equipment,and a lengthy wait time.For automatic glaucoma detection,state-of-the-art glaucoma detection methods include a segmentation-based method to calculate the cup-to-disc ratio.Other methods include multi-label segmentation networks and learning-based methods and rely on hand-crafted features.Localizing the optic disc(OD)is one of the key features in retinal images for detecting retinal diseases,especially for glaucoma disease detection.The approach presented in this study is based on deep classifiers for OD segmentation and glaucoma detection.First,the optic disc detection process is based on object detection using a Mask Region-Based Convolutional Neural Network(Mask-RCNN).The OD detection task was validated using the Dice score,intersection over union,and accuracy metrics.The OD region is then fed into the second stage for glaucoma detection.Therefore,considering only the OD area for glaucoma detection will reduce the number of classification artifacts by limiting the assessment to the optic disc area.For this task,VGG-16(Visual Geometry Group),Resnet-18(Residual Network),and Inception-v3 were pre-trained and fine-tuned.We also used the Support Vector Machine Classifier.The feature-based method uses region content features obtained by Histogram of Oriented Gradients(HOG)and Gabor Filters.The final decision is based on weighted fusion.A comparison of the obtained results from all classification approaches is provided.Classification metrics including accuracy and ROC curve are compared for each classification method.The novelty of this research project is the integration of automatic OD detection and glaucoma diagnosis in a global method.Moreover,the fusion-based decision system uses the glaucoma detection result obtained using several convolutional deep neural networks and the support vector machine classifier.These classification methods contribute to producing robust classification results.This method was evaluated using well-known retinal images available for research work and a combined dataset including retinal images with and without pathology.The performance of the models was tested on two public datasets and a combined dataset and was compared to similar research.The research findings show the potential of this methodology in the early detection of glaucoma,which will reduce diagnosis time and increase detection efficiency.The glaucoma assessment achieves about 98%accuracy in the classification rate,which is close to and even higher than that of state-of-the-art methods.The designed detection model may be used in telemedicine,healthcare,and computer-aided diagnosis systems.

Neuroprotective effects of resveratrol on retinal ganglion cells in glaucoma in rodents:A narrative review

Glaucoma,an irreversible optic neuropathy,primarily affects retinal ganglion cells(RGC)and causes vision loss and blindness.The damage to RGCs in glaucoma occurs by various mechanisms,including elevated intraocular pressure,oxidative stress,inflammation,and other neurodegenerative processes.As the disease progresses,the loss of RGCs leads to vision loss.Therefore,protecting RGCs from damage and promoting their survival are important goals in managing glaucoma.In this regard,resveratrol(RES),a polyphenolic phytoalexin,exerts antioxidant effects and slows down the evolution and progression of glaucoma.The present review shows that RES plays a protective role in RGCs in cases of ischemic injury and hypoxia as well as in ErbB2 protein expression in the retina.Additionally,RES plays protective roles in RGCs by promoting cell growth,reducing apoptosis,and decreasing oxidative stress in H_(2)O_(2)-exposed RGCs.RES was also found to inhibit oxidative stress damage in RGCs and suppress the activation of mitogen-activated protein kinase signaling pathways.RES could alleviate retinal function impairment by suppressing the hypoxia-i nducible factor-1 alpha/vascular endothelial growth factor and p38/p53 axes while stimulating the PI3K/Akt pathway.Therefore,RES might exert potential therapeutic effects for managing glaucoma by protecting RGCs from damage and promoting their survival.

The concept of gene therapy for glaucoma:the dream that has not come true yet

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in glaucoma.Since glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent manner.The most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic profile.The gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve crush-model.Reported gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,Com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,COX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

Neuroprotective effects of acteoside in a glaucoma mouse model by targeting Serta domain-containing protein 4

AIM:To explore the therapeutic effect and main molecular mechanisms of acteoside in a glaucoma model in DBA/2J mice.METHODS:Proteomics was used to compare the differentially expressed proteins of C57 and DBA/2J mice.After acteoside administration in DBA/2J mice,anterior segment observation,intraocular pressure(IOP)monitoring,electrophysiology examination,and hematoxylin and eosin staining were used to analyze any potential effects.Immunohistochemistry(IHC)assays were used to verify the proteomics results.Furthermore,retinal ganglion cell 5(RGC5)cell proliferation was assessed with cell counting kit-8(CCK-8)assays.Serta domain-containing protein 4(Sertad4)mRNA and protein expression levels were measured by qRT-PCR and Western blot analysis,respectively.RESULTS:Proteomics analysis suggested that Sertad4 was the most significantly differentially expressed protein.Compared with the saline group,the acteoside treatment group showed decreased IOP,improved N1-P1 wave amplitudes,thicker retina,and larger numbers of cells in the ganglion cell layer(GCL).The IHC results showed that Sertad4 expression levels in DBA/2J mice treated with acteoside were significantly lower than in the saline group.Acteoside treatment could improve RGC5 cell survival and reduce the Sertad4 mRNA and protein expression levels after glutamate injury.CONCLUSION:Sertad4 is differentially expressed in DBA/2J mice.Acteoside can protect RGCs from damage,possibly through the downregulation of Sertad4,and has a potential use in glaucoma treatment.

Baerveldt glaucoma implant with Supramid© ripcord stent in neovascular glaucoma: a case series

AIM:To report the outcome of Baerveldt glaucoma implant(BGI)with Supramid©ripcord use in neovascular glaucoma(NVG).METHODS:We retrospectively evaluated the surgical outcome of the BGI with Supramid©3/0 ripcord stent in patients with NVG.No tube ligation or venting slits were performed.Supramid was removed after 3mo if the target intraocular pressure(IOP)was not achieved.Surgical success was defined as IOP≤21 mm Hg with(qualified success)or without IOP-lowering medications(complete success).RESULTS:Twenty-six eyes from 24 patients were included in the study.The median duration of follow-up was 4[interquartile range(IQR)=1-5]y,ranging from 0.5 to 5y.IOP decreased by a mean of 24.2 mm Hg(59.7%);from a mean of 40.5±12.6 mm Hg at baseline to 16.3±11.9 mm Hg,P≤0.001.The number of glaucoma medications reduced from a median of 5(IQR=5-6)to 1(IQR=0-2,P≤0.001)at the final follow-up.Overall success rates were 88.0%at 1y,34.8%at 3y,66.7%at 4y,and 50%at 5y.Hypertensive phase(HP)in the first 3mo occurred in 15/26 eyes(57.7%)with a mean IOP of 31.1 mm Hg.CONCLUSION:BGI with Supramid©ripcord stent gives close to 90%of the overall survival rate at the final follow-up without significant early hypotony.However,early HP is still a challenge.

NMI,POLR3G and APIP are the key molecules connecting glaucoma with high intraocular pressure:a clue for early diagnostic biomarker candidates

AIM:To understand the molecular connectivity between the intraocular pressure(IOP)and glaucoma which will provide possible clues for biomarker candidates.METHODS:The current study uncovers the important genes connecting IOP with the core functional modules of glaucoma.An integrated analysis was performed using glaucoma and IOP microarray datasets to screen for differentially expressed genes(DEGs)in both conditions.To the selected DEGs,the protein interaction network was constructed and dissected to determine the core functional clusters of glaucoma.For the clusters,the connectivity of IOP DEGs was determined.Further,enrichment analyses were performed to assess the functional annotation and potential pathways of the crucial clusters.RESULTS:The gene expression analysis of glaucoma and IOP with normal control showed that 408 DEGs(277 glaucoma and 131 IOP genes)were discovered from two GEO datasets.The 290 DEGs of glaucoma were extended to form a network containing 1495 proteins with 9462 edges.Using ClusterONE,the network was dissected to have 12 clusters.Among them,three clusters were linked with three IOP DEGs[N-Myc and STAT Interactor(NMI),POLR3G(RNA Polymerase Ⅲ Subunit G),and APAF1-interacting protein(APIP)].In the clusters,ontology analysis revealed that RNA processing and transport,p53 class mediators resulting in cell cycle arrest,cellular response to cytokine stimulus,regulation of phosphorylation,regulation of type Ⅰ interferon production,DNA deamination,and cellular response to hypoxia were significantly enriched to be implicated in the development of glaucoma.Finally,NMI,POLR3G,and APIP may have roles that were noticed altered in glaucoma and IOP conditions.CONCLUSION:Our findings could help to discover new potential biomarkers,elucidate the underlying pathophysiology,and identify new therapeutic targets for glaucoma.

Penetrating canaloplasty in corticosteroid-induced glaucoma:a report of two cases

Dear Editor,We have treated two patients of glucocorticoid-induced glaucoma with penetrating canaloplasty(PCP)since 2021.PCP is a new type internal drainage surgery for glaucoma,which is a bleb-independent filtering surgery combined canaloplasty with trabeculectomy,and the surgery shows a great efficacy of intraocular pressure(IOP)reduction with no surgical complication.PCP surgery started with a fornix-based conjunctival flap and double scleral flap,and Schlemm’s canal was opened,a 10-0 prolene suture was positioned and tensioned within Schlemm’s canal,trabucular meshwork segment was excised and peripheral iridectomy was performed,the scleral flap and the conjunctival flap were closed watertight with 10-0 prolene sutures.