Simplifying “target” intraocular pressure for different stages of primary open-angle glaucoma and primary angle-closure glaucoma

Lowering of intraocular pressure is currently the only therapeutic measure for Glaucoma management. Many longterm, randomized trials have shown the efficacy of lowering IOP, either by a percentage of baseline, or to a specified level. This has lead to the concept of 'Target” IOP, a range of IOP on therapy, that would stabilize the Glaucoma/prevent further visual field loss, without significantly affecting a patient's quality of life. A clinical staging of Glaucoma by optic nerve head evaluation and perimetric parameters, allows a patient's eye to be categorized as having – mild, moderate or severe Glaucomatous damage. An initial attempt should be made to achieve the following IOP range for both POAG or PACG after an iridotomy. In mild glaucoma the initial target IOP range could be kept as 15-17 mmHg, for moderate glaucoma 12-15 mmHg and in the severe stage of glaucomatous damage 10-12 mmHg. Factoring in baseline IOP, age, vascular perfusion parameters, and change on perimetry or imaging during follow up, this range may be reassessed over 6 months to a year. “Target” IOP requires further lowering when the patient continues to progress or develops a systemic disease such as a TIA. Conversely, in the event of a very elderly or sick patient with stable nerve and visual field over time, the target IOP could be raised and medications reduced. An appropriate use of medications/laser/surgery to achieve such a “Target” IOP range in POAG or PACG can maintain visual fields and quality of life, preventing Glaucoma blindness.

Clinical and epidemiological study in patients with primary open-angle glaucoma / Estudo clínico-epidemiológico em indivíduos com glaucoma primário de ângulo aberto

Abstract Objective: To evaluate the clinical and epidemiological profile of patients with primary open-angle glaucoma. Methods: This is a quantitative study with cross-sectional and analytical design, which sample consisted of 425 patients treated in an unit of Specialized Care in Ophthalmology, located in the northern state of Minas Gerais, from 2004 to 2015. We collected the data using formularies that addressed demographic and clinical aspects, risk factors and the presence of undercurrent diseases. We conducted an ophthalmological examination to evaluate anatomical and functional changes. We used statistical analysis, and the results are presented by mean, standard deviation and percentiles 25, 50 and 75. Results: Females predominate (56.8%), the age group of 60 years or older (44%) and mixed skin (81.7%). A minority of participants present risk factors such as high myopia (6.3%) and diabetes mellitus (17.9%). Regarding the clinical examination, there is a prevalence of increased optic nerve excavation (≥ 0.8) and low thickness of the corneas (≤ 535 microns). Conclusion: Most people develop advanced glaucoma, with increased optic nerve excavation and changed visual fields. Other common risk factors are: family history of glaucoma, decreased thickness of the cornea and hypertension. Early diagnosis and treatment can prevent vision loss. Primary care physicians should consider referring patients who have glaucoma risk factors, for an ophthalmologic examination.

Resumo Objetivo: Avaliar o perfil clínico-epidemiológico dos indivíduos com glaucoma primário de ângulo aberto. Métodos: Trata-se de estudo quantitativo com desenho transversal e analítico, mediante amostra constituída de 425 pacientes atendidos em uma Unidade de Atenção Especializada em Oftalmologia localizada no norte do estado de Minas Gerais, Brasil, cadastrados no período de 2004 a 2015. As variáveis analisadas foram: características demográficas e clínicas, fatores de risco e presença de doenças associadas. Foi realizado exame oftalmológico para avaliar alterações anatômicas e funcionais. Para as análises estatísticas foram utilizados os programas Statistical Package for the Social Sciences (SPSS), versão 19.0. Considerou-se nível de significância p<0,05 para as variáveis categóricas. As variáveis descritivas foram apresentadas pela média, desvio-padrão e percentis 25, 50 e 75. Resultados: Predominou o gênero feminino (56,8%), a faixa etária de 60 anos ou mais (44%), e a cor da pele parda (81,7%). Fatores de risco como alta miopia (6,3%) e diabetes mellitus (17,9%) foram relatados pela minoria dos participantes. Em relação ao exame clínico, houve prevalência de escavação do nervo óptico aumentada (≥ 0,8 mm2) e baixa espessura central das córneas (≤ 535 micras). Conclusão: A maioria dos indivíduos apresenta glaucoma avançado, com escavações do nervo óptico aumentadas e campos visuais alterados. Outros fatores de risco frequentes foram: história familiar positiva para glaucoma, espessura central da córnea diminuída e hipertensão arterial sistêmica. Diagnóstico e tratamento precoces podem prevenir contra a perda de visão no glaucoma. Médicos da atenção primária à saúde devem encaminhar os pacientes que tenham fatores de risco para glaucoma, para a consulta especializada e exames oftalmológicos.

Advances in genetic study of primary open angle glaucoma / 中华实验眼科杂志

Primary open angle glaucoma (POAG) is a complex and heterogeneous neurodegenerative disease caused by genetic and environmental factors,and it is also one of the leading causes of irreversible blindness worldwide.Recent molecular genetic studies revealed that numbers of susceptible gene variants are associated with POAG,and the researching technology includes genome wide association study and whole exon sequence.Studies of POAG families discovered 16 loci linked to the disease.To date,three genes were reported to be the causative genes of POAG,they are these studies MYOC,OPTN and WDR36.Other causative or presumably causative genes are thought to contribute to POAG,such as NTF4 and TBK1.Genetic factor for the path ogenesis POAG is being widely concerned,and provides a solid foundation for genetic research and gene therapy of this disease.In this paper,we reviewed a comprehensive discussion of the genetics and research strategies of POAG.

Therapeutic effects of induced pluripotent stem cells on primary open angle glaucoma / 中华实验眼科杂志

Glaucoma is an group of ocular disease associated with the degeneration of retinal ganglion cells and it finally causes vision loss.Primary open angle glaucoma (POAG) is a main type of glaucoma worldwide.The primary reason of POAG is elevated intraocular pressure (lOP) caused by the degeneration or dysfunction of the trabecular meshwork (TM).Recent studies showed that stem cell-based therapy becomes a promising approach to treat the degenerative diseases,including POAG.Among multiple types of stem cells,induced pluripotent stem cell (iPSC) is the one with the most clinical potential due to its autologous derivation and non-ethical issue.In this paper,we summarized the encouraging therapeutic effects of iPSCs on POAG from different species,different etiological factors and different pathological stages.Although these encouraging studies suggest that iPSC is a fabulous stem cell type to regenerate the damaged tissue,more efforts are required for clinical application.In addition,we discussed several solutions to improve the safety of iPSCs and provided potential approaches to improve the therapeutic efficiency and specific targeting.Answering these questions will help us to better understand the characteristics of iPSCs and promote the development of bench to bedside research.

Evaluation of macular ganglion cell complex and peripheral retinal nerve fiber layer structural damage in early primary glaucomous eyes by 3D-OCT / 中华实验眼科杂志

Background In previous study,peripheral retinal nerve fiber layer (RNFL) thickness is considered to be the earliest structural changes which can be detected.3D-OCT can measure the thickness of macular ganglion cell complex (mGCC),which makes the detection of primary glaucoma possible in the early stage.Objective This study was to measure the thickness of mGCC and disc-peripheral RNFL in early stage of primary glaucomous eyes by 3D-OCT and assess the anatomic basis of glaucoma-induced optical nerve damage.Methods 3D-OCT images from 10 patients with advanced stage primary glaucoma in one lateral eye and early stage glaucoma in fellow eye from December 2010 to December 2012 were prospectively analyzed in China-Japan Friendship Hospital.The patients were diagnosed based on the recommended standard of National glaucoma group (1987 version) and received routine eye examination.3D-OCT scanning was performed using 3D-macular mode,3D-macular Wide mode and 3D-disc mode with TOPCON 3D-OCT 2000 system,and the images at macular 6 mm×6 mm area were analyzed.The posterior pole area was divided into 5 concentric rings from fovea toward periphery and equally subdivided into 100 small checks,with the area of 0.6 mm×0.6 mm for each.The probable values in each check were calculated as the ratio of each figure and corresponding normal value.The probable values were expressed as red color (P＜ 1％),yellow color (P＜5％) and gray color (P≥ 5％).Then the disc-periphery RNFL thickness and disc cup were evaluated.Results No evident abnormality was found in the thicknesses of photoreceptors layer and bipolar cell layer in both advanced glaucomous eyes and the early stage of glaucomous eyes in the 10 patients.Serious damage of visual field was seen in the advanced glaucomous eyes and presented with red color in the parapapillary RNFL area,mGCC area and macular RNFL area,showing an evidently attenuation of the thicknesses of parapapillary RNFL,mGCC and RNFL.However,the visual field was close normal in the early stage glaucomous eyes,and mGCC and macular RNFL showed yellow color,while green or yellow color was exhibited in the parapapillary RNFL area,indicating mGCC and macular RNFL thickness was reduced,but parapapillar RNFL thickness was near normal.Conclusions The change of mGCC thickness is earlier than that of peripheral RNFL at optic disc in primary glaucomaous eyes,which may imply that the disappear of macular ganglion cell body is earlier than that of the axon.

A pilot study of the relationship between retinal structural and functional damage in primary open-angle glaucoma / 中华实验眼科杂志

Background Application of available technology and objective indexes are very important for the early diagnosis,monitoring and therapeutic evaluation of primary open angle glaucoma (POAG).Many studies have determined retinal damage in structure and function in POAG.However,the study on the association of structural damage and functional abnormality in early POAG is still lack.Objective This study was to evaluate the relationship between structural and functional changes of retina in early stage of POAG.Methods A prospectively pilot study was performed under the approval of Ethic Committee of Shenzhen Eye Hospital from January 2011 to June 2013.Based on Helsinki Declaration,written informed consent was obtained from subject prior to entering the cohort.Ninety-five eyes of 95 POAG patients were included as the study group,and 41 eyes of 41 non-glaucoma subjects were enrolled at the same period as controls.The structural parameters of retinas were measured using RTVue-100 OCT and Cirrus HD-OCT respectively,including macular ganglion cell complex (GCC)-Avg thickness and peripapillary retinal neural fibril layer (RNFL)-Avg thickness;and the functional parameters of retinas were obtained by Humphrey visual filed analyzer and RETI scan 3.15 system respectively,including MD of visual field and PhNR of flash electroretinogram (F-ERG).The associations between the GCC or RNFL thickness and M D or amplitude of PhNR were evaluated by linear and curvilinear regression models.Results The MD,GCC-Avg,RNFL-Avg and PhNR amplitude were (-0.68±1.72)dB,(97.17± 4.82)μm,(102.51±8.74) μm and (49.61±11.01)μV respectively in the control subjects,and those in the POAG patients were (-10.82±9.87) dB,(75.07±12.29) μm,(69.09±12.96) μm and (28.38± 11.52) μV,showing significant differences between them (t =6.549,11.118,-15.061,9.956,all at P=0.001).The curvilinear regression model appeared to better describe the relationship between GCC thickness and MD (R2 =0.595,F=97.089,P＜0.001) ;while a linear regression model seemed to be better fit for the relationship between GCC thickness and amplitude of PhNR (R2=0.437,F=103.413,P＜0.001).RNFL thickness analysis showed the similar regression models with MD and amplitude of PhNR as GCC thickness,but R2 values were higher between the RNFL thickness and MD (R2 =0.606,F =101.666,P＜0.001) or amplitude of PhNR (R2 =0.454,F=54.983,P＜0.001).Conclusions Both GCC thickness and RNFL thickness show a curvilinear relationship with MD and a linear relationship with amplitude of PhNR.Goodness-of-fit of RNFL thickness is superior to GCC thickness.

Multicenter clinical study of safety and efficacy of selective laser trabeculoplasty for Chinese primary open angle glaucoma / 中华实验眼科杂志

Background Selective laser trabeculoplasty (SLT) is a safe and effective therapy to the treatment of primary open angle glaucoma (POAG),and the clinical application is approved by American FDA.However,the relevant researching outcomes from several single-center study are in dispute owing to non-uniform approach in China.A muhicenter clinical trial is need to verify the effectiveness of SLT for Chinese POAG.Objective This study was to investigate the safety and efficacy of SLT in Chinese POAG patients.Methods A prospective,multicenter and self-controlled clinical trail was designed.Sixty-two eyes of 62 POAG patients with the age of ≥ 18 years were enrolled.Frequency SLT was performed around 360° angle using Lumenis Selecta DuetTM or Lumenis Selecta Ⅱ laser instrument,with the 100 non-overlapping spots,3 ns preset time,400 μm size of laser spot and 0.6 mJ energy.The operated eyes were followed-up for 6 months.The curative effects were checked including intraocular pressure (IOP),IOP-lowing value,number and percentage of IOP-lowing 20％ and 30％.The therapyrelated complications were recorded including the number of conjunctival congestion and cloudy of the anterior chamber.Results The preoperative IOP was (25.7±2.6) mmHg in the 62 eyes.The IOP was significantly lowed 1 day,2 weeks,4 weeks,3 months and 6 months after SLT in comparison with preoperative IOP (all at P＜0.001) with the lowest value of (16.5±4.5)mmHg in postoperative day 1.IOP was stable from 4 weeks to 6 months after operation.The mean lowing-value of IOP was 5.3-9.2 mmHg from 1 day through 6 months after SLT.The percentage of eyes 20％ drop in lOP was 83.9％,and that of 30％ drop was 58.1％ in postoperative day 1.In 6 months after SLT,percentages of eyes 20％ and 30％ drop in IOP were 56.5％ and 27.4％,respectively.Conclusions SLT is a safe and effective method of lowing IOP for POAG eyes in Chinese population.

The flow cytometry of trabecular meshwork cells apoptosis in Monglia with primary angle closure glaucoma / 中华实验眼科杂志

Background Research showed that the morbidity rate of primary angle closure glaucoma (PACG) in Mongolian population is 3.02 times more than Han nationality population.To understand the cause and mechanism of PACG in Mongolia is of an important significance.Objective This study was to investigate the pathogenesis of Mongolian PACG.Methods Thirty-two eyes of 32 PACG patients in Mongolia and 40 eyes of 40 PACG patients of Han peoples were included in Inner Mongolia Autonomous Region People's Hospital according to the diagnosis criteria of glaucoma group of Chinese Medical Ophthalmology Association (version 1987),and 13 eyes of 13 normal Mongolia and 17 eyes of 17 normal Han peoples who suffered with ocular truma were recruited as controls.Intraocular pressure(IOP) was measured before surgery.The trabecular meshwork tissue was obtained from all the eyes during the operation.Annexinv-FITC/PI double staining was performed and the apoptosis rate of trabecula cells was tested with flow cytometry.Written informed consent was obtained initial of the study.Results The IOP value in Mongolia PACG group,Han PACG group,Mengolia normal group and Han normal group was (35.97±7.11)mmHg,(38.70± 6.82) mmHg,(14.69 ± 2.91) mmHg and (13.59 ± 2.91) mmHg,respectively,showing a significant difference among the 4 groups(F=106.144,P=0.000),and the IOP was significantly higher in the Mengolia PACG group and Han PACG group than the normal groups(P＜0.05).The apoptosis rate of the cells was (7.14±0.67)％,(5.40±0.69) ％,(5.86±0.91) ％ and(2.29±0.65) ％ in the Mongolia PACG group,Han PACG group,Mongolia normal group and Han normal group,respectively,with a significant difference among them (F =174.888,P =0.000),and apoptosis rate of the Mongolia PACG group was significantly higher than that of the Han PACG group and the Mongolia normal group (P＜0.05).No significant difference was found between the Mongolia PACG group and the Han PACG group or between the Mongolia normal group and Han normal group (P＞0.05).The cell apoptosis rate was increased with the elevation of IOP (b =0.990,F=10.209,P =0.009) with the regression equition Y =2.788 +0.092X.Conclusions The apoptosis rate of trabecula cells in Mongolian is higher than Han people.If these results are associated with the high incidence of Mengolia PACG is worth of study.

The advances of lens extraction for primary angle closure glaucoma / 中华实验眼科杂志

Development of primary angle closure glaucoma (PACG) is closely related to the changes of the position and morphology of the lens owing to a shallow anterior chamber,pupillary blockage and angle closure.Lens extraction can deepen the depth of the anterior chamber and resolve the pupillary blockage,and therefore increase the outflow of aqueous fluid.Furthermore,the combination of lens extraction with goniosynechialysis can reopen the closed anterior chamber angle and relieve peripheral anterior synechia of pupil,with a better clinical effectiveness for primary angle closure glaucoma.Recently,the studies related to lens extraction for primary angle closure glaucoma have madc great progression,especially its mechanism and efficacy,and of course some existing problems of lens extraction are concerned.In this review,the relationship between lens and primary angle closure glaucoma,the clinical effectiveness of lens extraction for primary angle closure glaucoma,the safety evaluation of lens extraction and goniosynechialysis were summarized.