|Year : 2018 | Volume
| Issue : 3 | Page : 197-200
R K Eye Care Centre, Rasipuram, Tamil Nadu, India
|Date of Web Publication||23-Oct-2018|
R K Eye Care Centre, Rasipuram, Namakkal, Tamil Nadu
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Vasumathi R. Journal scan. TNOA J Ophthalmic Sci Res 2018;56:197-200
Alio JL, Rodriguez AE, Ferreira-Oliveira R, Wróbel-Dudzińska D, Abdelghany AA. Treatment of dry eye disease with autologous platelet-rich plasma: A prospective, interventional, non-randomized study. Ophthalmol Ther 2017;6:285-93.
Autologous serum (AS) has been suggested as a treatment for severe dry eye disease (DED) over preservative-free artificial molecules, with variable success rates. Platelet-rich plasma (PRP) and plasma rich in growth factors have also been reported as successful treatments for moderate-to-severe dry eye, presenting advantages over AS due to its richer concentration of growth factors, anti-inflammatory cytokines, and other platelet derivatives, which could be beneficial for the required ocular surface restoration in moderate-to-severe forms of dry eye. Autologous PRP is a hemoderivative with a high concentration of platelets obtained through a relatively simple process, which requires minimal manipulation and no addition of any other particular substance. A recent study has shown that these components help in the proliferation, migration, and differentiation of corneal epithelial cells. Monotherapy with autologous PRP eye drops has shown to be a very good option for the treatment of moderate-to-severe chronic DED. Significant advantages are ease of preparation, the absence of preservatives, its autologous origin, safety, and minimal or no intolerance.
The objective of this study was to evaluate the use of autologous PRP eye drops as monotherapy for the treatment of moderate-to-severe cases of DED. Three hundred and sixty-eight patients with moderate-to-severe DED were included in this prospective case series. Patients were classified as evaporative DED (EDED) or aqueous deficient DED (ADDED). Improvement of the DED subjective symptoms, corneal fluorescein staining (CFS), and corrected distance visual acuity (BCVA) were evaluated. It was also analyzed how many rounds of PRP therapy were used. Two hundred and ninety-seven (80.7%) patients were women and 71 (19.3%) were men. Two hundred and thirty-two (63%) patients had EDED, whereas 136 (37%) had ADDED. After 6 weeks of monotherapy treatment with autologous PRP, dry eye symptoms improved in 322 (87.5%) cases. A decrease of CFS was observed in 280 (76.1%) patients. One hundred and six (28.8%) patients improved at least 1 line of BCVA. The scores in the Ocular Surface Disease Index and the Oxford scale of corneal fluorescein staining decreased statistically after the treatment (P< 0.05).
Take home message
The topical use of autologous PRP as monotherapy is an effective treatment to improve signs and symptoms in patients suffering from moderate-to-severe chronic DED.
Kita T, Clermont AC, Murugesan N, Zhou Q, Fujisawa K, Ishibashi T, et al. Plasma Kallikrein-Kinin system as a VEGF-independent mediator of diabetic macular edema. Diabetes 2015;64:3588-99.
This study characterized the kallikrein-kinin system in vitreous from individuals with diabetic macular edema (DME) and examined mechanisms contributing to retinal thickening and retinal vascular permeability (RVP). Plasma prekallikrein (PPK) and plasma kallikrein (PKal) were increased 2- and 11.0-fold (both P < 0.0001), respectively, in vitreous from patients with DME compared to those with macular hole (MH). While vascular endothelial growth factor (VEGF) was also increased in DME vitreous, PKal and VEGF concentrations did not correlate (r = 0.266, P = 0.112). Using mass spectrometry-based proteomics, they identified 167 vitreous proteins, including 30 that were increased in DME (≥4-fold, P < 0.001 vs. MH). The majority of proteins associated with DME displayed a higher correlation with PPK than with VEGF concentrations. DME vitreous containing relatively high levels of PKal and low VEGF-induced RVP when injected into the vitreous of diabetic rats, a response blocked by bradykinin receptor antagonism but not by bevacizumab. Bradykinin-induced retinal thickening in mice was not affected by blockade of VEGF-R2. Diabetes-induced RVP was decreased by up to 78% (P< 0.001) in Klkb1 (PPK)-deficient mice compared with wild-type controls. B2 and B1 receptor-induced RVP in diabetic mice was blocked by endothelial nitric oxide synthase (eNOS)-and inducible NOS-deficiency, respectively. These findings implicate the PKal pathway as a VEGF-independent mediator of DME.
Take home message
KKS is increased in human DME vitreous. Klkb1 deficiency in mice decreased DM-induced RVP, and the effects of the BK on retinal thickening did not require VEGFR2. Both B1R and B2R contribute to the effects of the KKS on retinal thickening and RVP, and these responses are mediated by eNOS and iNOS, respectively. These findings suggest that the intraocular KKS may contribute to DME via a VEGF-independent mechanism.
Teufel DP, Bennett G, Harrison H, van Rietschoten K, Pavan S, Stace C, et al. Stable and long-lasting, novel bicyclic peptide plasma kallikrein inhibitors for the treatment of diabetic macular edema. J Med Chem 2018;61:2823-36.
Plasma kallikrein, a member of the kallikrein-kinin system, catalyzes the release of the bioactive peptide bradykinin, which induces inflammation, vasodilation, vessel permeability, and pain. Preclinical evidence implicates the activity of plasma kallikrein in diabetic retinopathy, which is a leading cause of visual loss in patients suffering from diabetes mellitus. Employing a technology based on phage display combined with chemical cyclization, the authors have identified highly selective bicyclic peptide inhibitors with nano- and picomolar potencies toward plasma kallikrein. Stability in biological matrices was either intrinsic to the peptide or engineered via the introduction of nonnatural amino acids and nonpeptidic bonds. The peptides prevented bradykinin release in vitro, and in vivo efficacy was revealed in both a rat paw edema model and in rodent models of diabetes-induced retinal permeability. These peptides had a highly extended half-life of ∼40 h in rabbit eyes following intravitreal administration.
Take home message
The bicyclic peptides, plasma kallikrein inhibitors, are promising novel agents for the treatment of diabetic retinopathy and diabetic macular edema.
Hamdan HZ, Nasser NM, Adam AM, Saleem MA, Elamin MI. Serum magnesium, iron and ferritin levels in patients with diabetic retinopathy attending Makkah eye complex, Khartoum, Sudan. Biol Trace Elem Res 2015;165:30-4.
Diabetic retinopathy is the most common complications of diabetes mellitus that, in most occasions, lead to blindness. Multiple evidences linked the serum magnesium, iron and ferritin disturbance with diabetes and its complications. A case–control study was conducted at Makkah Eye Complex, Khartoum, Sudan, to compare the levels of serum magnesium, iron and ferritin in patients with diabetic retinopathy with diabetic patients without diabetic retinopathy (controls). Findings indicate that all patients had type 2 diabetes. The two groups (50 in each arm) were well matched in their basic characteristics. Median (25th–75th interquartile) of serum magnesium in patients with diabetic retinopathy were significantly lower than patients without diabetic retinopathy (1.48 [0.75–1.64] vs. 1.92 [1.4–2.3] mg/dl, P = 0.022). The median of serum iron and ferritin was lower in cases than control group but did not reach a statistical significance (20.5 [17.2–48.0] vs. 27.0 [16.0–54.0] μg/dl, P = 0.568; 98.0 [45.0–134.75] vs. 101.0 [47.0-161.0] μg/L, P = 0.818). The duration of diabetes (16.5 [9.3] vs. 11.2 [6.6] years; P = 0.014) and hemoglobin level (13.7 [0.9] vs. 12.5 [2.0] g/dl; P = 0.039) were significantly higher in cases group than control group. A significant inverse correlation was observed between serum magnesium and iron levels. Twenty (40%) patients had severe nonproliferative diabetic retinopathy with mild macular edema, which is the most prevalent type among the cases group.
Take home message
Hypomagnesemia among diabetic patients was associated with diabetic retinopathy, while serum iron and ferritin had no significant effect in this setting.
Yang L, Li S, Miao L, Huang H, Liang F, Teng X, et al. Rescue of glaucomatous neurodegeneration by differentially modulating neuronal endoplasmic reticulum stress molecules. J Neurosci 2016;36:5891-903.
Neuron soma and axon degeneration have distinct molecular mechanisms although they are clearly connected after axon injury. Axon injury is an early event in neurodegenerative diseases that often leads to retrograde neuronal cell death and progressive, permanent loss of vital neuronal functions. The connection of these two obviously sequential degenerative events, however, is elusive. Deciphering the upstream signals that trigger the neurodegeneration cascades in both neuronal soma and axon would be a key step toward developing the effective neuroprotectants that are greatly needed in the clinic. It was shown previously that optic nerve injury-induced neuronal endoplasmic reticulum (ER) stress plays an important role in retinal ganglion cell (RGC) death. Using two in vivo mouse models of optic neuropathies (traumatic optic nerve injury and glaucoma) and adeno-associated virus–mediated RGC-specific gene targeting, the authors have shown that differential manipulation of unfolded protein response pathways in opposite directions – inhibition of eukaryotic translation initiation factor 2α-C/enhancer binding protein homologous protein and activation of X-box binding protein 1 – promoted both RGC axons and somata survival and preserved visual function.
Take home message
The results indicate that axon injury-induced neuronal ER stress plays an important role in both axon degeneration and neuron soma death. Neuronal ER stress is, therefore, a promising therapeutic target for glaucoma and potentially other types of neurodegeneration.
Nordström M, Schiller M, Fredriksson A, Behndig A. Refractive improvements and safety with topography-guided corneal crosslinking for keratoconus: 1-year results. Br J Ophthalmol 2017;101:920-5.
The purpose of this study was to assess the refractive improvements and the corneal endothelial safety of an individualized topography-guided regimen for corneal crosslinking in progressive keratoconus. An open-label prospective randomized clinical trial was performed at the Department of Clinical Sciences, Ophthalmology, Umeå University Hospital, Umeå, Sweden. Thirty-seven patients (50 eyes) with progressive keratoconus planned for corneal crosslinking were included. The patients were randomized to topography-guided crosslinking (photorefractive intrastromal crosslinking [PiXL]; n = 25] or uniform 9-mm crosslinking (corneal collagen crosslinking [CXL]; n = 25). Visual acuity, refraction, keratometry (K1, K2, and Kmax), and corneal endothelial morphometry were assessed preoperatively and at 1, 3, 6 and 12 months postoperatively. The PiXL treatment involved an asymmetrical treatment zone-centered on the area of maximum corneal steepness with treatment energies ranging from 7.2 to 15.0 J/cm2; the CXL treatment was a uniform 9 mm 5.4 J/cm2 pulsed crosslinking. The main outcome measures were changes in refractive errors and corneal endothelial cell density. The spherical refractive errors decreased (P< 0.05) and the visual acuity improved (P< 0.01) at 3, 6, and 12 months after PiXL, but not after CXL. The between-group differences, however, were not significant. K2 and Kmax decreased at 3, 6, and 12 months after PiXL (P< 0.01), but not after CXL (P< 0.01 when comparing the two treatments). No corneal endothelial cell loss was seen after either treatment.
Take home message
Individualized topography-based crosslinking treatment centered on the ectatic cone has the potential to improve the corneal shape in keratoconus with decreased spherical refractive errors and improved visual acuity, without damage to the corneal endothelium.
Tang TB, Bhatti M, Laude A. Effects of water drinking test on blood flow in optic nerve head using LSFG. Investig Ophthalmol Vis Sci 2015;56:2743.
Water drinking test (WDT) has been proposed, because of its simplicity, as a potential diagnostic test for glaucoma based on the considerable effect on intraocular pressure, which is an important risk factor. Furthermore, it has been established that optic nerve blood flow is a risk factor for glaucoma, and literature suggests a reduced ocular blood flow in glaucoma patients. Therefore, optic nerve head (ONH) blood flow monitoring is of high importance in glaucoma. The purpose of the study was to investigate whether WDT has any effect on ONH blood flow, despite the autoregulation phenomenon. Laser speckle flowgraphy (LSFG) is a noninvasive modality which calculates mean blur rate (MBR) of ocular blood flow and provides insight on pulse waveform of heartbeat. Various pulse waveform parameters, such as skew, blowout score (BOS), and blowout time (BOT) in the ONH can be estimated. This experiment involved 5 healthy controls, who were asked to refrain from eating, drinking, or smoking for 2 h before the experiment began. The patients were seated in a comfortable experiment room with room temperature being regulated at 25°C. Initial LSFG reading was taken as a baseline, then the patients were asked to drink 1 liter of water. LSFG readings were recorded at 5, 10, 15, 20, 25, 30, 40, 50, and 60 min after the water intake. MBR of ONH, skew, BOT, and BOS were examined for all the patients. Five patients participated in the experiment, and their measurements were normalized. The averaged result of heartbeat using error bars with standard deviations was plotted. The results showed a slight reduction, although not found to be statistically significant, in all pulse waveforms parameters examined during analysis.
Take home message
The results showed that healthy controls exhibited autoregulation of blood flow. Although the sample size was limited, the results may provide an important baseline for comparison with glaucoma patients, where a disrupted blood flow causes autoregulation dysfunction in ONH.
Daien V, Le Pape A, Heve D, Carriere I, Villain M. Incidence, risk factors, and impact of age on retinal detachment after cataract surgery in France: A national population study. Ophthalmology 2015;122:2179-85.
The aim of this cohort study was to assess the incidence, risk factors, and impact of age on retinal detachment (RD) after cataract surgery. All patients older than 40 years of age who underwent a primary cataract surgery in France between January 2009 and December 2012 were included in the study. A Cox proportional-hazard regression model was used to analyze risk factors of RD after cataract surgery. Over 4 years, 2,680,167 eyes in 1787021 patients (59.4% women; mean age, 73.9 ± 9.5 years) underwent cataract surgery. A total of 11,424 patients experienced RD after cataract surgery, with an estimated risk of 0.99% at 4 years after surgery. The odds ratio associated with increased risk of RD was 3.87 (95% confidence interval [CI], 3.79–3.95) for cataract surgery itself. The multiadjusted hazard ratio (HR) associated with increased risk of RD was 5.22 (95% CI, 5.05–5.39) for patients 40–54 years of age, 3.69 (95% CI, 3.60–3.79) for those 55–64 years of age, and 1.98 (95% CI, 1.93–2.03) for those 65–74 years of age as compared with those 75 years of age or older. Retinal detachment was associated with high myopia (HR, 6.12; 95% CI, 5.84–6.41), vitrectomy for perioperative capsular rupture (HR, 4.36; 95% CI, 4.07–4.68), history of eye trauma (HR, 3.98; 95% CI, 3.69–4.30), extracapsular extraction (HR, 3.11; 95% CI, 2.94–3.30), male gender (HR, 2.39; 95% CI, 2.35–2.44), and history of diabetes (HR, 1.18; 95% CI, 1.15–1.21). In myopic patients, the multiadjusted HR associated with increased risk of RD was 25.02 (95% CI, 24.76–25.18) for patients 40–54 years of age, 20.37 (95% CI, 20.21–20.53) for those 55–64 years of age, and 17.05 (95% CI, 16.85–17.25) for those 65–74 years of age as compared with nonmyopic patients 75 years of age or older.
Take home message
The hierarchy of risk factors for RD onset: high myopia, young age, capsular rupture, history of eye trauma, extracapsular extraction technique, male gender, and diabetes. Young age was an additional risk factor in myopic patients.
Noguchi C, Koseki H, Horiuchi H, Yonekura A, Tomita M, Higuchi T, et al. Factors contributing to airborne particle dispersal in the operating room. BMC Surg 2017;17:78.
Surgical-site infections due to intraoperative contamination are chiefly ascribable to airborne particles carrying microorganisms. The purpose of this study was to identify the actions that increase the number of airborne particles in the operating room. Two surgeons and two surgical nurses performed three patterns of physical movements to mimic intraoperative actions, such as preparing the instrument table, gowning and donning/doffing gloves, and preparing for total knee arthroplasty. The generation and behavior of airborne particles were filmed using a fine particle visualization system, and the number of airborne particles in 2.83 m3 of air was counted using a laser particle counter. Each action was repeated five times, and the particle measurements were evaluated through one-way analysis of variance multiple comparison tests followed by Tukey–Kramer and Bonferroni–Dunn multiple comparison tests for post hoc analysis. Statistical significance was defined as a value of P ≤ 0.01. A large number of airborne particles were observed while unfolding the surgical gown, removing gloves, and putting the arms through the sleeves of the gown. Although numerous airborne particles were observed while applying the stockinet and putting on large drapes for preparation of total knee arthroplasty, fewer particles (0.3–2.0 μm in size) were detected at the level of the operating table under laminar airflow compared to actions performed in a nonventilated preoperative room (P< 0.01).
Take home message
The results of this study suggest that surgical staff should avoid unnecessary actions that produce a large number of airborne particles near a sterile area and that laminar airflow has the potential to reduce the incidence of bacterial contamination.
Shu DY, Wojciechowski MC, Lovicu FJ. Bone morphogenetic protein-7 suppresses TGFβ2-induced epithelial-mesenchymal transition in the lens: Implications for cataract prevention. Invest Ophthalmol Vis Sci 2017;58:781-96.
Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a key pathologic mechanism underlying cataract. Two members of the transforming growth factor-β (TGFβ) superfamily, TGFβ and bone morphogenetic protein-7 (BMP-7) have functionally distinct roles in EMT. While TGFβ is a potent inducer of EMT, BMP-7 counteracts the fibrogenic activity of TGFβ. This study examined the modulating effect of BMP-7 on TGFβ-induced EMT in LECs. Rat lens epithelial explants were treated exogenously with TGFβ2 alone or in combination with BMP-7 for up to 5 days. Expression levels of E-cadherin, β-catenin, α-smooth muscle actin (α-SMA), and phosphorylated downstream Smads were determined using immunofluorescence and Western blotting. Reverse transcriptase quantitative polymerase chain reaction was used to study gene expression levels of EMT markers and downstream BMP target genes, including the inhibitors of differentiation (Id). Transforming growth factor-β2 induced LECs to transdifferentiate into myofibroblastic cells. Addition of BMP-7 suppressed TGFβ2-induced α-SMA protein levels and mesenchymal gene expression, with retention of E-cadherin and β-catenin expression to the cell membrane. Addition of BMP-7 prevented lens capsular wrinkling and cellular loss associated with TGFβ2-induced EMT over the 5-day treatment period. The inhibitory effect of BMP-7 was accompanied by an early induction of pSmad1/5 and suppression of TGFβ2-induced pSmad2/3. Treatment with TGFβ2 alone suppressed gene expression of Id2/3 and addition of BMP-7 restored Id2/3 expression.
Take home message
Exogenous administration of BMP-7 abrogated TGFβ2-induced EMT in rat lens epithelial explants. Understanding the complex interplay between the TGFβ-and BMP-7–associated Smad signaling pathways and their downstream target genes holds therapeutic promise in cataract prevention.
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Conflicts of interest
There are no conflicts of interest.