Progress of clinical therapies for dry age-related macular degeneration

Dry age-related macular degeneration(AMD)is a progressive blinding disease that currently affects millions of people worldwide with no successful treatment available.Significant research efforts are currently underway to develop therapies aimed at slowing the progression of this disease or,more notably,reversing it.Here the therapies which have reached clinical trial for treatment of dry AMD were reviewed.A thorough search of Pub Med,Embase,and Clinicaltrials.gov has led to a comprehensive collection of the most recent strategies being evaluated.This review also endeavors to assess the status and future directions of therapeutics for this debilitating condition.     

Overflow phenomenon in serum lutein after supplementation: a systematic review supported with SNPs analyses

Lutein, a type of carotenoids, is found to delay the onset and progression of age-related macular degeneration (AMD). Several lutein supplementation studies showed that after an initial increase, lutein serum levels demonstrated a subsequent decrease despite continuous supplementation. In this systematic literature review, this obscure phenomenon was tried to be explained. The subsequent drop in lutein levels was postulated due to down-regulation of lutein receptors scavenger receptor class B type I (SR-BI) in the gastrointestinal tract, upregulation of lutein degrading enzyme β-carotene dioxygenase (BCDO2), or perhaps a combination of both. Some single nucleotides polymorphisms (SNPs) that could have influence on the occurrence of this phenomenon. To date, an exact scientific explanation for this phenomenon has not been established. Further research is needed to investigate this phenomenon in depth to reach an irrefutable explanation, giving that lutein is proven to be effective in delaying the onset and progression of AMD and its metabolism in the human body becomes of equal importance.     

Immunologic mechanism of fungal keratitis

Lutein, a type of carotenoids, is found to delay the onset and progression of age-related macular degeneration (AMD). Several lutein supplementation studies showed that after an initial increase, lutein serum levels demonstrated a subsequent decrease despite continuous supplementation. In this systematic literature review, this obscure phenomenon was tried to be explained. The subsequent drop in lutein levels was postulated due to down-regulation of lutein receptors scavenger receptor class B type I (SR-BI) in the gastrointestinal tract, upregulation of lutein degrading enzyme β-carotene dioxygenase (BCDO2), or perhaps a combination of both. Some single nucleotides polymorphisms (SNPs) that could have influence on the occurrence of this phenomenon. To date, an exact scientific explanation for this phenomenon has not been established. Further research is needed to investigate this phenomenon in depth to reach an irrefutable explanation, giving that lutein is proven to be effective in delaying the onset and progression of AMD and its metabolism in the human body becomes of equal importance.     

TRPC6: an underlying target for human glaucoma

Glaucoma is one of the leading causes of visual impairment and blindness worldwide. Of known risk factors for glaucoma, an increased in intraocular pressure is most highly correlated with glaucomatous damage. Irrespective of the cause, apoptosis of the retinal ganglion cells is the eventual outcome. It is widely accepted that glaucoma is a neurodegenerative disease that is strongly correlated with central nervous system disorders, such as Alzheimer’s disease. These two disorders also share some similarities in pathogenic mechanisms. Recent studies suggest that the transient receptor potential canonical 6 channel could work together with brain-derived neurotrophic factor to promote neuron survival in brain and retina. In this study, we propose that transient receptor potential canonical 6 may contribute to the pathogenesis of human glaucoma and become a potential therapeutic target.     

Treatment options for the wet form of age-related macular degeneration-a perspective

Treatment of the wet form of age-related macular degeneration (wet AMD) has been revolutionized a decade ago with the introduction of vascular endothelial growth factor (VEGF) blockers that reduce neovascularization and macular edema. Two approved drugs are marketed for the treatment of wet AMD—ranibizumab and alfibercept, but there is a third drug, bevacizumab, which is widely used off-label; a cancer drug that also blocks VEGF but was never tested in pivotal trials and never approved for ophthalmic indications including wet AMD. Similarity of bevacizumab to ranibizumab led to off-label use and even to government-sponsored studies comparison the approved ranibizumab head-to-head to the off-label cancer drug bevacizumab in wet AMD, like the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) study, discussed in this perspective paper. Recent publication of 5-year follow-up from the initial 2-year CATT study provided the occasion to discuss the similarities and differences between these two drugs and the lessons learned from the last decade of anti-VEGF therapy for wet AMD. Clinical efifcacy is comparable, with an advantage for ranibizumab. Likewise, safety ifnding favor ranibizumab over bevacizumab in some aspects. The latest addition of approved anti-VEGF drugs for wet AMD, alfibercept, may provide even more beneift to patients. In this perspective we discuss results of CATT and other long-term follow-up and comparative studies. While all demonstrate clinical beneift of anti-VEGF, all reveal that most patients’ loose visual acuity (VA) in real-life situations over 5–7 years. This loss is based on—what we believe—significant under-treatment of wet AMD patients, due to economic or practical limitations and overestimation of perceived risks as geographic atrophy. We compare own data that showed more intensive treatment (more than twice the CATT-follow-up injections) with ranibizumab or alfibercept can maintain a sustained gain in VA in wet AMD patients after 6 years. We encourage retina specialists to treat wet AMD patients more aggressively and frequently in order to provide the maximum beneift for their patients.     

Tests for malingering in ophthalmology

Simulation can be defined as malingering, or sometimes functional visual loss (FVL). It manifests as either simulating an ophthalmic disease (positive simulation), or denial of ophthalmic disease (negative simulation). Conscious behavior and compensation or indemnity claims are prominent features of simulation. Since some authors suggest that this is a manifestation of underlying psychopathology, even conversion is included in this context. In today’s world, every ophthalmologist can face with simulation of ophthalmic disease or disorder. In case of simulation suspect, the physician’s responsibility is to prove the simulation considering the disease/disorder first, and simulation as an exclusion. In simulation examinations, the physician should be firm and smart to select appropriate test(s) to convince not only the subject, but also the judge in case of indemnity or compensation trials. Almost all ophthalmic sensory and motor functions including visual acuity, visual field, color vision and night vision can be the subject of simulation. Examiner must be skillful in selecting the most appropriate test. Apart from those in the literature, we included all kinds of simulation in ophthalmology. In addition, simulation examination techniques, such as, use of optical coherence tomography, frequency doubling perimetry (FDP), and modified polarization tests were also included. In this review, we made a thorough literature search, and added our experiences to give the readers up-to-date information on malingering or simulation in ophthalmology.     

New options for uveitis treatment

Simulation can be defined as malingering, or sometimes functional visual loss (FVL). It manifests as either simulating an ophthalmic disease (positive simulation), or denial of ophthalmic disease (negative simulation). Conscious behavior and compensation or indemnity claims are prominent features of simulation. Since some authors suggest that this is a manifestation of underlying psychopathology, even conversion is included in this context. In today’s world, every ophthalmologist can face with simulation of ophthalmic disease or disorder. In case of simulation suspect, the physician’s responsibility is to prove the simulation considering the disease/disorder first, and simulation as an exclusion. In simulation examinations, the physician should be firm and smart to select appropriate test(s) to convince not only the subject, but also the judge in case of indemnity or compensation trials. Almost all ophthalmic sensory and motor functions including visual acuity, visual field, color vision and night vision can be the subject of simulation. Examiner must be skillful in selecting the most appropriate test. Apart from those in the literature, we included all kinds of simulation in ophthalmology. In addition, simulation examination techniques, such as, use of optical coherence tomography, frequency doubling perimetry (FDP), and modified polarization tests were also included. In this review, we made a thorough literature search, and added our experiences to give the readers up-to-date information on malingering or simulation in ophthalmology.     

Potential role of retina as a biomarker for progression of Parkinson’s disease

Optical coherence tomography (OCT) noninvasively quantifies the thickness of the retinal nerve fiber layer (RNFL). OCT has been studied in several neuro-ophthalmic conditions, including Parkinson’s disease (PD). Recent studies suggest that the quantitative analysis of RNFL can be precisely and noninvasively done by OCT scans and the results suggest that the thickness of RNFL is significantly decreased in patients with PD compared with age-matched controls and the foveal retinal thickness correlates with disease severity in PD. In this article, the application of OCT imaging of the retina in PD was reviewed. Literature survey of PubMed was carried out using the search terms of “Optical Coherence Tomography” combined with “Parkinson’s Disease” and “retinal nerve fiber layer” (without restriction to the year of publication). Some related articles were also included. The search was completed in Jul. 2011 and revised and updated as necessary. The aim of this article is to review the current literatures on the use of optical coherence tomography in patients affected by PD and to enhance its use in clinical practice in neuro-ophthalmology.     

An Immunologic Study on Age-related Macular Degeneration

Forty-one patients with age-related macular degeneration(AMD) were detected for serum autoantibodies against normal humanretinal protein by means of Western immunoblot analysis.Twenty-sevenout of the 41 patients showed positive response,with a rate of 66 percent.The positive rate of antiretinal antibody in the AMD patients wassignificantly higher than that in normal controls (18%) and in patients withother retinal diseases (24%) (p<0.0005).These antiretinal antibodies fromthe AMD patients partly reacted with the retinal protein of molecular weightbetween 28 and 32 Kd,partly with Mr of 38 to 42 Kd,48 to 52 Kd,62 to65 Kd or 110 to 130 Kd.Of them,the antiretinal antibody against theprotein with Mr of 28 to 32 Kd in the AMD patients was higher than innormal controls (p<0.05).Two or more antibodies were found in theserum from AMD patients,showing a significant difference between thepatients and the controls (p<0.005).The results indicated that in theoccurrence of AMD and/or during its developing process there wereinflammation and immunological response,involving antibodies againstretinal proteins of various molecular weight.Eye Science 1993;9:113-120.     

Glaucoma secondary to trabecular meshwork precipitates: a case report of Grant’s syndrome

AIM: To describe a via pars plana anterior iris enclavation IOL fixation technique. METHODS: A total of 35 consecutive aphakic vitrectomised patients (average age 71±7.14y) underwent pars plana vitrectomy (PPV) and via pars plana anterior iris enclavation IOL fixation. RESULTS: The mean preoperative best corrected visual acuity (BCVA) was 0.11±0.14 logMAR, the mean post-operative BCVA was 0.07±0.11 logMAR. The preoperative mean spherical equivalent was 7.22±4.21. The final mean spherical equivalent was -0.25±0.15. No eyes had hypotony, retinal or choroidal detachment or endophthalmitis. CONCLUSION: This technique may be a safe and useful in the case of aphakia, and a prospective study would be useful to confirm this findings.     

IOL repositioning using iris sutures: a safe and effective technique

This retrospective non-comparative consecutive case series study was conducted at Azienda Ospedaliera Universitaria Careggi, Florence, Italy and describes a useful intraocular lens (IOL) repositioning technique using iris sutures. In our study, 41 consecutive cases of posteriorly dislocated IOLs were surgically treated between January 2015 and May 2017. Six of the cases were post-traumatic luxations, and 20 patients had pseudoexfoliation syndrome. All the patients underwent pars plana vitrectomy and same IOL repositioning using iris sutures. The mean follow-up was 12.2mo. The mean preoperative best corrected visual acuity (BCVA) was 0.10±0.15 logMAR, whereas the mean postoperative BCVA was 0.08±0.14 logMAR. The mean postoperative BCVA did not change significantly from the preoperative BCVA. The final mean spherical equivalent was -0.44±0.49 SD. Three lenses (7.31%) were found tilted during post-operative follow-up. Two eyes (4.87%) had postoperative cystoid macular edema. No eyes had endophthalmitis, hypotony, retinal or choroidal detachment. The iris fixation technique seems to be a safe and valid option for the management of dislocated IOLs.     

Surgical outcomes and complications of sutureless needle-guided intrascleral intraocular lens fixation combined with vitrectomy

Purpose:To analyze the surgical outcomes and complications of sutureless needle-guided intrascleral intraocular lens (IOL) implantation (Yamane technique) combined with pars plana vitrectomy.Methods:Retrospective study of 47 eyes of 46 patients that underwent scleral fixation of IOL by the Yamane technique combined with 3-port pars plana vitrectomy. Demographic data, primary indications for surgery, history of trauma, best corrected visual acuity (BCVA), intraocular pressure (IOP), duration of follow-up, and complications were analyzed.Results:Mean preoperative BCVA was 0.79 logMAR, which improved to 0.39 logMAR at mean 4.21 months (SD: 4.87 D) follow-up. Mean spherical equivalent pre and postoperative was + 7.64 D (SD: 7.74 D) and − 0.47 D (SD: 2.26 D), respectively. Early postoperative complications included hypotony with cyclodialysis cleft (n = 1; 2%), mild vitreous hemorrhage (n = 2; 4%), raised IOP (n = 2; 4%), and transient corneal edema (n = 2; 4%). Late complications included iris optic capture (n = 1; 2%), retinal detachment (n = 1; 2%), cystoid macular edema (CME; n = 2; 4%), IOL decentration (n = 1; 2%), and decentration and tilting of IOL (n = 1; 2%). Management of complications included laser treatment to cyclodialysis cleft, observation for vitreous hemorrhage, topical and oral IOP lowering agents for raised IOP. CME was managed with topical non-steroidal anti-inflammatory drugs. One eye was subjected IOL refixation. The mean number of surgeries per eye was 1.04.Conclusion:Combining needle-guided intrascleral IOL implantation with vitrectomy allows management of other posterior segment complications in the same sitting while obviating the need for the second surgery. It provides satisfactory outcomes that are comparable to published studies. However, a longer follow-up will allow a better understanding of the potential advantages of this approach.     

Early clinical outcome with a new monofocal microincision intraocular lens

The purpose of this study was to evaluate the early visual and refractive outcomes of a new aspheric monofocal microincision intraocular lens (IOL). This retrospective case series included eyes of patients who underwent implantation of a microincision IOL following 1.8 mm manual coaxial microincision cataract surgery and who attended regular postoperative follow-up visits on the first week and first, third, and sixth months. The postoperative uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), refraction and predictability, intraoperative and postoperative complications, posterior capsule opacification (PCO), IOL centration, and surgically induced astigmatism (SIA) were evaluated. Sixty-three eyes of 38 patients ranging in age from 51 to 86 were included in the study. The mean preoperative BCVA was 0.52 ± 0.42 logMAR. At the postoperative sixth month, the mean postoperative UCVA and BCVA were 0.12 ± 0.11 and 0.01 ± 0.03 logMAR, respectively. The mean postoperative spherical equivalent refraction (SER) was ?0.30 ± 0.49 D. The SER was within ± 1.00 D of the attempted correction in 95.2 % of the eyes. The mean SIA measured with vector analysis was 0.45 ± 0.28 D. Mild PCO was observed in 9 eyes (14.7 %) with none requiring Nd:Yag laser capsulotomy. On centration analysis, the IOL was found to be 0.26 mm on average to the supero-nasal position. The aspheric microincision IOL was safely implanted and provided satisfactory visual and refractive outcomes in the early postoperative period.     

25G PPV联合IOL睫状沟缝合固定置换术治疗IOL囊袋复合体脱位于玻璃体腔

目的：评估25G玻璃体切割(PPV)联合人工晶状体(IOL)睫状沟缝合固定置换术治疗IOL囊袋复合体脱位于玻璃体腔的临床效果。

方法：回顾性分析我院2015-01/2020-01应用25G玻璃体切割联合IOL睫状沟缝合固定置换术治疗IOL囊袋复合体完全脱位于玻璃体腔的患者21例21眼的临床资料。

结果：所有患者术中均顺利取出脱位的IOL复合体,未出现医源性视网膜损伤,术中发现视网膜裂孔4眼,视网膜格子样变性2眼,分别予以视网膜激光光凝。随访6～18mo,BCVA(LogMAR)由术前的0.40±0.30提高到术后的0.33±0.25(P=0.040)。所有病例末次随访BCVA均达到术前BCVA。术后等效球镜度与术前IOL屈光度预测值相差的绝对值≤0.75D。末次随访时所有患者IOL位置良好,未发生视网膜脱离等并发症。

结论：25G玻璃体切割联合IOL睫状沟缝合固定置换手术是治疗IOL囊袋复合体脱位安全有效的方法。     

Transscleral fixation of a foldable intraocular lens in aphakic vitrectomized eyes

PURPOSE: To evaluate the clinical outcomes of transscleral fixation of a foldable intraocular lens (IOL) in eyes that had pars plana lensectomy combined with pars plana vitrectomy for severe vitreoretinal disease. SETTING: Seoul National University Hospital, Seoul, Korea. METHODS: The medical records of 21 patients who had a transscleral fixation of a foldable IOL after previous vitrectomy combined with lensectomy for severe posterior segment pathology were reviewed. The underlying vitreoretinal diseases were complicated proliferative diabetic retinopathy (n = 9), proliferative vitreoretinopathy (n = 5), traumatic retinal detachment (n = 3), intraocular foreign body (n = 2), and uveitic retinal detachment (n = 2). The postoperative best corrected visual acuity (BCVA) was compared with the preoperative BCVA. Autorefractometry and keratometry measurements and central endothelial cell counts were evaluated 1 day preoperatively and 6 months postoperatively. RESULTS: The mean age of the patients was 54.5 years. The preoperative aphakic period ranged from 2 to 22 months. The visual acuity reached the preoperative BCVA by 2 months after surgery and was better than the preoperative BCVA at 6 months (P =.006) and at the final visit (P =.003). Six months postoperatively, the mean myopic shift by cycloplegic autorefractometry was -1.0 diopter (D) and the mean scalar shift in surgically induced keratometric cylinder, 1.0 D. The mean central corneal endothelial loss at 6 months was 6.7% (range 2.4% to 22.2%). The only vitreoretinal complications were a transient vitreous hemorrhage and a reopened macular hole that was reattached after fluid-gas exchange. CONCLUSION: Transscleral fixation of a foldable IOL was safe and led to favorable visual outcomes in aphakic vitrectomized eyes with previous severe vitreoretinal disease.     

两种单焦点人工晶状体经睫状体平坦部巩膜缝线固定术后视觉质量的比较

目的：探究2种不同类型单焦点人工晶状体（IOL）经睫状体平坦部巩膜缝线固定术后视觉质量的差异。方法：回顾性系列病例研究。选取2019年6月至2020年6月就诊于潍坊眼科医院因外伤导致无法囊袋内植入IOL的患者42例（42眼）,所有患者均接受二期经睫状体平坦部IOL巩膜缝线固定术,其中植入ZeissCTLucia601PY单焦点后房型IOL25例（25眼）作为601PY组;植入AQBH单焦点后房型IOL17例（17眼）作为AQ组。术后随访6~12个月,观察2组患者手术前后的最佳矫正视力（BCVA）、调制传递函数截止频率（MTFcutoff）、客观散射指数（OSI）、等效球镜度（SE）等差异。数据采用Mann-WhitneyU秩和检验、独立样本t检验进行分析。结果：601PY组、AQ组患者手术前、后BCVA差异均无统计学意义（Z=-1.39,P=0.164;Z=-0.36,P=0.721）。2组术后BCVA差异无统计学意义（Z=-1.24,P=0.215）。2组术后MTF cutoff、OSI值差异有统计学意义（t=2.15,P=0.043; t=-2.22,P=0.038）。2组术后SE差异无统计学意义（Z=-0.65,P=0.517）。结论：单焦点IOL经睫状体平坦部巩膜缝线固定术可获得较好的视力和视觉质量,但不同类型单焦点IOL术后视觉质量存在差异,其中ZeissCTLucia601PYIOL略优于AQBHIOL。     

Photorefractive keratectomy after cataract surgery in uncommon cases: long-term results

AIM: To evaluate the efficacy and safety of the excimer laser correction of the residual refractive errors after cataract extraction with intraocular lens (IOL) implantation in uncommon cases. METHODS: Totally 24 patients with high residual refractive error after cataract surgery with IOL implantation were examined. Twenty-two patients had a history of phacoemulsification and IOL implantation, and two had extra-capsular cataract extraction with IOL implantation. Detailed examination of preoperative medical records was done to explain the origin of the post-cataract refractive errors. All patients underwent photorefractire keratectomy (PRK) enhancement. The mean outcome measures were refraction, uncorretted visual acuity (UCVA), best corrected visual acuity (BCVA) and corneal transparency and follow up ranged from 1 to 8y. RESULTS: The principal causes of residual ametropia was inexact IOL calculation in abnormal eyes with high myopia and congenital lens abnormalities, followed by corneal astigmatism both suture induced and preexisting. After cataract surgery and before the laser enhancement the mean spherical equivalent (SE) was -0.56±3 D ranging from -4.62 to +2.25 D in high myopic patients, instead it was -1±1.73 D ranging from -3.25 to +3.75 D in the astigmatic eyes, with a mean cylinder of -3.75±0 ranging from -3 to +5.50 D. After laser refractive surgery the mean SE was 0.1±0.73, ranging from -0.50 to +1.50 in the myopic group, and it was -0.50±0.57 ranging from -1.25 to +0.50 in astigmatic patients, with a mean cylinder of -0.25±0.75. In myopic patients the mean UCVA and BCVA were 0.038±0.072 logMAR and 0.018±0.04 respectively, both ranging from 0.10 to 0.0. In astigmatic patients, the mean UCVA and BCVA were 0.213±0.132 and 0.00±0.0 respectively, UCVA ranging from 0.50 to 0.22 and BCVA was 0.00. All patients presented normal corneal transparency. No ocular hypertension was detected and no corneal haze was observed. All registered values remained stable also at the end line evaluation. CONCLUSION: The excimer laser treatment of residual refractive errors after cataract surgery with IOL implantation in abnormal eyes resulted in satisfactory and stable visual outcome with good safety and efficacy.     

Foldable iris‐fixated intraocular lens implantation in children

Purpose: To describe the results of foldable iris‐fixated intraocular lens (IOL) implantation in children. Methods: Children with high bilateral or unilateral myopia who were intolerant of spectacle or contact lens correction were implanted with an iris‐fixated foldable IOL and prospectively followed. We measured pre‐ and postoperative visual acuity, refraction, endothelial cell density (ECD) and National Eye Institute Visual Functioning Questionnaire‐25. Results: Eleven eyes of six children were implanted. Indications were high bilateral myopia in children with comorbid neurobehavioural disorders, high anisometropia and high myopic astigmatism. Mean preoperative spherical equivalent (SE) refraction was ?14.6 dioptres (D) ± 4.2 SD. Mean follow‐up was 15 months. Postoperative SE refraction was ?2.40 D ± 2.40 SD. Corrected distance visual acuity (CDVA) improved from mean logMAR 0.84 ± 0.4 SD to postoperative 0.67 ± 0.34 SD (p = 0.005). CDVA was reduced because of coexistent ocular disorders and amblyopia. Vision‐related quality of life (QOL) measures improved significantly. There were no intraoperative or postoperative serious complications. Conclusion: Foldable iris‐fixated IOL insertion can give a significant improvement in vision and in vision‐related QOL in a subset of paediatric patients with special refractive needs who are intolerant to conventional treatment. Long‐term follow‐up is required for monitoring of ECD.     

Outcomes of secondary sulcus intraocular lens implantation in unilateral anterior persistent fetal vasculature

AIM: To evaluate the surgical results of sulcus intraocular lens (IOL) implantation in children with unilateral anterior persistent fetal vasculature (PFV) underwent primary vitrectomy combined with lensectomy and preservation of the peripheral anterior capsule. METHODS: Twenty-two eyes of 22 children with unilateral anterior PFV who underwent sulcus secondary IOL implantation were analyzed. Main outcome measures were preoperative and postoperative visual acuity, and complications both intraoperatively and postoperatively. RESULTS: Review of 22 consecutive patients identified best-corrected visual acuity (BCVA) improvement from 1.37±0.84 to 0.73±0.57 logarithm of the minimal angle of resolution (logMAR) after IOL implantation (P<0.001) with a mean follow-up was 16.55±5.86mo. Average age at secondary IOL implantation was 41.05±15.41mo. Three eyes (13.64%) achieved BCVA of 0.3 logMAR at the final visit. Transient intraocular pressure rise (4 eyes; 18.18%), postoperative increased inflammation (3 eyes; 13.64%) and postoperative hypotony (2 eyes; 9.09%) were common complications. CONCLUSION: Properly preservation of the anterior lens capsule during the primary surgery facilitated secondary sulcus IOL implantation in pediatric patients with anterior PFV, with favorable postoperative visual outcomes and compatible percentage of complications.