Laser treatment in diabetic retinopathy

Diabetic retinopathy is a leading cause of visual impairment and blindness in developed countries due to macular edema and proliferative diabetic retinopathy (PDR). For both complications laser treatment may offer proven therapy: the Diabetic Retinopathy Study demonstrated that panretinal scatter photocoagulation reduces the risk of severe visual loss by >= 50% in eyes with high-risk characteristics. Pan-retinal scatter coagulation may also be beneficial in other PDR and severe nonproliferative diabetic retinopathy (NPDR) under certain conditions. For clinically significant macular edema the Early Treatment of Diabetic Retinopathy Study could show that immediate focal laser photocoagulation reduces the risk of moderate visual loss by at least 50%. When and how to perform laser treatment is described in detail, offering a proven treatment for many problems associated with diabetic retinopathy based on a high evidence level. Copyright (c) 2007 S. Karger AG, Basel

Interaction of Bestrophin-1 and Ca2+ Channel β-Subunits: Identification of New Binding Domains on the Bestrophin-1 C-Terminus

Bestrophin-1 modulates currents through voltage-dependent L-type Ca2+ channels by physically interacting with the β-subunits of Ca2+ channels. The main function of β-subunits is to regulate the number of pore-forming CaV-subunits in the cell membrane and modulate Ca2+ channel currents. To understand the influence of full-length bestrophin-1 on β-subunit function, we studied binding and localization of bestrophin-1 and Ca2+ channel subunits, together with modulation of CaV1.3 Ca2+ channels currents. In heterologeous expression, bestrophin-1 showed co-immunoprecipitation with either, β3-, or β4-subunits. We identified a new highly conserved cluster of proline-rich motifs on the bestrophin-1 C-terminus between amino acid position 468 and 486, which enables possible binding to SH3-domains of β-subunits. A bestrophin-1 that lacks these proline-rich motifs (ΔCT-PxxP bestrophin-1) showed reduced efficiency to co-immunoprecipitate with β3 and β4-subunits. In the presence of ΔCT-PxxP bestrophin-1, β4-subunits and CaV1.3 subunits partly lost membrane localization. Currents from CaV1.3 subunits were modified in the presence of β4-subunit and wild-type bestrophin-1: accelerated time-dependent activation and reduced current density. With ΔCTPxxP bestrophin-1, currents showed the same time-dependent activation as with wild-type bestrophin-1, but the current density was further reduced due to decreased number of Ca2+ channels proteins in the cell membrane. In summary, we described new proline-rich motifs on bestrophin-1 C-terminus, which help to maintain the ability of β-subunits to regulate surface expression of pore-forming CaV Ca2+-channel subunits

Potassium Channel and NKCC Cotransporter Involvement in Ocular Refractive Control Mechanisms

Myopia affects well over 30% of adult humans globally. However, the underlying physiological mechanism is little understood. This study tested the hypothesis that ocular growth and refractive compensation to optical defocus can be controlled by manipulation of potassium and chloride ion-driven transretinal fluid movements to the choroid. Chicks were raised with +/−10D or zero power optical defocus rendering the focal plane of the eye in front of, behind, or at the level of the retinal photoreceptors respectively. Intravitreal injections of barium chloride, a non-specific inhibitor of potassium channels in the retina and RPE or bumetanide, a selective inhibitor of the sodium-potassium-chloride cotransporter were made, targeting fluid control mechanisms. Comparison of refractive compensation to 5mM Ba2+ and 10−5 M bumetanide compared with control saline injected eyes shows significant change for both positive and negative lens defocus for Ba2+ but significant change only for negative lens defocus with bumetanide ; ; ; ; ; ). Vitreous chamber depths showed a main effect for drug conditions with less depth change in response to defocus shown for Ba2+ relative to Saline, while bumetanide injected eyes showed a trend to increased depth without a significant interaction with applied defocus. The results indicate that both K channels and the NKCC cotransporter play a role in refractive compensation with NKCC blockade showing far more specificity for negative, compared with positive, lens defocus. Probable sites of action relevant to refractive control include the apical retinal pigment epithelium membrane and the photoreceptor/ON bipolar synapse. The similarities between the biometric effects of NKCC inhibition and biometric reports of the blockade of the retinal ON response, suggest a possible common mechanism. The selective inhibition of refractive compensation to negative lens in chick by loop diuretics such as bumetanide suggests that these drugs may be effective in the therapeutic management of human myopia

Systemic 7-methylxanthine in retarding axial eye growth and myopia progression: a 36-month pilot study

The adenosine antagonist 7-methylxanthine (7-mx) works against myopia in animal models. In a clinical trial, 68 myopic children (mean age 11.3 years) received either placebo or 7-mx tablets for 12 months. All participants subsequently received 7-mx for another 12 months, after which treatment was stopped. Axial length was measured with Zeiss IOL-Master and cycloplegic refraction with Nikon Retinomax at −6, 0, 12, 24, and 36 months. Axial growth was reduced among children treated with 7-mx for 24 months compared with those only treated for the last 12 months. Myopia progression and axial eye growth slowed down in periods with 7-mx treatment, but when the treatment was stopped, both myopia progression and axial eye growth continued with invariable speed. The results indicate that 7-mx reduces eye elongation and myopia progression in childhood myopia. The treatment is safe and without side effects and may be continued until 18–20 years of age when myopia progression normally stops

Photodynamic therapy combined with antivascular endothelial growth factor treatment for recalcitrant chronic central serous chorioretinopathy

Masumi G Asahi,1 Andrew T Chon,1 Esmeralda Gallemore,1 Ron P Gallemore1,2 1Clinical Research Department, Retina Macula Institute, Torrance, CA, USA; 2Jules Stein Eye Institute, University of California, Los Angeles, CA, USA Purpose: To determine whether combination photodynamic therapy (PDT) and antivascular endothelial growth factor (VEGF) therapy is effective in the management of chronic central serous chorioretinopathy (CSC) recalcitrant to conventional therapy. Methods: This was a retrospective analysis of eight patients with chronic CSC unresponsive to topical nonsteroidal anti-inflammatory drugs, focal photocoagulation, anti-VEGF alone, or PDT alone. All patients were evaluated with a full ophthalmic examination, spectral-domain optical coherence tomography (OCT), fluorescein angiography (FA), and most with indocyanine green angiography (ICGA) followed by treatment with half-fluence PDT and intravitreal anti-VEGF injection (seven bevacizumab, one aflibercept). Patients were seen in follow-up 1 month after treatment. Results: All eight patients achieved complete resolution in subretinal fluid following combination treatment. Average duration of CSC prior to initiation of combination therapy was 7.5 months. Mean central macular thickness on OCT decreased significantly from 401.2±52.7 µm to 297.9±18.2 µm (p=0.0010) by 4 months after treatment (1.63±1.18 months). Seven of eight patients were followed up for an average of 13 months with no recurrence during that time. One case recurred at 8 months and was treated with repeat combination at that time. Frank choroidal neovascularization (CNV) was not identified in these cases on FA or ICGA studies. Eight of eight patients showed significant improvement in vision from a logMAR of 0.1125±0.099 to 0.0125±0.064 (p=0.019). Conclusion: Combination PDT and anti-VEGF is effective for chronic CSC which has failed conventional therapy. Associated CNV and/or inflammation may be reasons for greater success in patients treated with combination therapy. Keywords: anti-VEGF, chronic central serous chorioretinopathy, combination, photodynamic therapy, recalcitran

Acute macular edema following intracorporeal prostaglandin injection for erectile dysfunction

Masumi G Asahi, Calvin Chou, Ron P Gallemore Retina Macula Institute, Torrance, CA, USA Purpose: We aimed to describe the first case of macular edema following intracorporeal injection of alprostadil, a prostaglandin E1. Methods: This was a retrospective case report followed with optical coherence tomography, fundus photos, and fluorescein angiography images. Results: A patient developed bilateral cystoid macular edema following intracorporeal injection of alprostadil, a prostaglandin E1 for treatment of erectile dysfunction. The edema resolved following treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, with subsequent recovery in visual acuity. Discussion: Systemic prostaglandin administration can cause macular edema and vision loss, indicating that elevated systemic prostaglandin levels may affect visual function. This has potential implications for other systemic disorders and treatments that could affect macular function. Keywords: alprostadil, inflammatio

Chloride currents in acutely isolated Xenopus retinal pigment epithelial cells

The retinal pigment epithelium (RPE) regulates the ionic composition of the fluid surrounding the photoreceptors by transport mechanisms that utilize Cl− channels. Cl− currents in RPE cells, however, remain incompletely characterized. The purpose of this study was to identify the Cl− currents in acutely isolated Xenopus RPE cells using whole-cell patch clamp. We describe three different Cl− currents. (1) An inwardly rectifying Cl− current, ICl,ir, activates slowly with hyperpolarization (τact=μ1 s at −80 mV, V1/2=−94 ± 3 mV), is blocked by Zn2+ (IC50=185 μm), is stimulated by acid (ICl,ir is 5 times larger at pH 6 than pH 8), and is blocked by DIDS in a voltage-dependent manner. ICl,ir closely resembles cloned ClC-2currents. (2) An outwardly rectifying Cl− current, ICl,Ca, is stimulated by elevated cytosolic free [Ca2+]. With 1 μm free [Ca2+]i in the patch pipette, ICl,Ca activates slowly with depolarization (τact=325 ms at 100 mV) and deactivates upon hyperpolarization. ICl,Ca is not blocked by 1 mm Zn2+ or 10 μm Gd3+ but is blocked by DIDS. High extracellular [Ca2+] (10 mm) also activates ICl,Ca. (3) A non-rectifying current is activated by elevation of cytoplasmic cAMP with forskolin and IBMX. In addition to these three Cl− currents, Xenopus RPE cells exhibit a non-selective background current (Ibkg) which has a linear I-V relationship and is voltage insensitive. This current is blocked by Zn2+ (IC50 of 5.3 μm) or 10 μm Gd3+. This description provides new insights into the physiology of Cl− channels involved in salt and fluid transport by the retinal pigment epithelium

Topical difluprednate for the treatment of Harada’s disease

Spencer M Onishi, Masumi G Asahi, Calvin Chou, Ron P Gallemore Retina Macula Institute, Torrance, CA, USA Purpose: To describe the use of topical difluprednate for treatment of patients who presented with Harada’s disease.Methods: Retrospective case series of patients managed with topical difluprednate alone at the onset of the diagnosis. The patients were followed with optical coherence tomography (OCT) and fluorescein angiography.Results: In our three cases, complete resolution of the exudative detachments with improvement in visual acuity was achieved in each case. Central macular thickness was reduced by a mean of 365±222 µm. Initial loading dose was one drop every hour while awake, followed by a variable tapering regimen. Leakage on fluorescein angiography and exudative detachments on OCT both responded to treatment with difluprednate. In two of the three cases, the patients recovered vision to 20/20, and the third case recovered to 20/25. Steroid-induced glaucoma was observed and managed with one to two glaucoma drops as needed.Conclusion: Difluprednate is effective for managing ocular manifestations of Harada’s disease. Further studies of this drug for the management of noninfectious posterior uveitis are warranted. Keywords: serous retinal detachment, noninfectious posterior uveitis, steroi

Strong topical steroid, NSAID, and carbonic anhydrase inhibitor cocktail for treatment of cystoid macular edema

Masumi G Asahi, Gabriela L Bobarnac Dogaru, Spencer M Onishi, Ron P GallemoreRetina Macula Institute, Torrance, CA, USA Purpose: To report the combination cocktail of strong steroid, non-steroidal anti-inflammatory drug (NSAID), and carbonic anhydrase inhibitor drops for treatment of cystoid macular edema. Methods: This is a retrospective case series of patients with cystoid macular edema managed with a topical combination of strong steroid (difluprednate), NSAID, and carbonic anhydrase inhibitor drops. The patients were followed with optical coherence tomography and fluorescein angiography. Results: In our six cases, resolution of the cystic edema with improvement in visual acuity was achieved with the use of a combination cocktail of drops. Leakage on fluorescein angiography and cystic edema on optical coherence tomography both responded to treatment with the topical cocktail of drops. Conclusion: A topical cocktail of strong steroid, NSAID, and carbonic anhydrase inhibitor drops are effective for managing cystoid macular edema. Further studies comparing this combination with more invasive treatments should be undertaken to determine the efficacy of this cocktail over other treatment options. Keywords: birdshot chorioretinopathy, diabetic macular edema, retinal vein occlusio

Combination verteporfin photodynamic therapy ranibizumab-dexamethasone in choroidal neovascularization due to age-related macular degeneration: results of a phase II randomized trial

Ron P Gallemore,1 Josh Wallsh,1 Henry L Hudson,2 Allen C Ho,3 Richard Chace,4 Joel Pearlman5 On behalf of the RADICAL Trial Group 1Retina Macula Institute, Torrance, CA, 2Retina Centers PC, Tucson, AZ, 3Wills Eye Institute, Philadelphia, PA, 4Eyesight Ophthalmic Services, Portsmouth, NH, 5Retinal Consultants Medical Group, Sacramento, CA, USA Purpose: To assess whether combination therapy (CT) reduces retreatments when compared to ranibizumab monotherapy (RM), while safely maintaining similar vision outcomes. Methods: In this 24-month trial, patients with age-related macular degeneration (AMD) were randomized to 1) quarter-fluence or 2) half-fluence triple therapy (verteporfin photodynamic therapy [vPDT] + ranibizumab + dexamethasone), 3) half-fluence double therapy (vPDT + ranibizumab), or 4) RM. The primary outcomes were number of retreatment visits and change from baseline in visual acuity (VA) at 12 months. Results: One hundred sixty-two subjects enrolled. There were 4.0 (P=0.02), 3.2 (P<0.001), 4.1 (P=0.03), and 5.7 retreatment visits through month 12, and 5.9 (P=0.03), 4.3 (P<0.001), 5.9 (P=0.02) and 8.7 through month 24, in groups 1, 2, 3, and 4, respectively (P-value comparing with RM). Month 12 VA score change from baseline (95% confidence interval) was +3.6 (–0.9 to +8.1), +6.8 (+2.4 to +11.1), +5.0 (+0.6 to +9.3), and +6.5 (+1.7 to +11.4), respectively. Conclusion: CT resulted in significantly fewer retreatment visits than a RM regimen at months 12 and 24. VA results appeared similar although wide confidence intervals preclude conclusions regarding vision outcomes. Keywords: age-related macular degeneration (AMD), combination therapy, ranibizumab, photodynamic therapy (PDT), verteporfi