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Purpose To quantify retinal capillary density and morphology in uveitis using spectral-domain optical coherence tomography angiography (SD-OCTA). Design Cross-sectional, observational study. Methods Healthy and uveitic subjects were recruited from 2 tertiary care eye centers. Prototype SD-OCTA devices (Cirrus; Carl Zeiss Meditec, Inc, Dublin, California, USA) were used to generate 3 × 3-mm 2 OCTA images centered on the fovea. Subjects were placed into 3 groups based on the type of optical microangiography (OMAG) algorithm used for image processing (intensity and/or phase) and type of retinal segmentation (automatic or manual). A semi-automated method was used to calculate skeleton density (SD), vessel density (VD), fractal dimension (FD), and vessel diameter index (VDI). Retinal vasculature was assessed in the superficial retinal layer (SRL), deep retinal layer (DRL), and nonsegmented retinal layer (NS-RL). A generalized estimating equations model was used to analyze associations between the OCTA measures and disease status within each retinal layer. A P value Results The SD, VD, and FD of the parafoveal capillaries were lower in uveitic eyes compared with healthy eyes in all retinal segments. In addition, SD and VD were significantly lower in the DRL of subjects with uveitic macular edema. There was no correlation in any capillary parameters and anatomic classification of uveitis. Conclusions Quantitative analysis of parafoveal capillary density and morphology in uveitis demonstrates significantly lower capillary density and complexity. SD-OCTA algorithms are robust enough to detect these changes and can provide a novel diagnostic index of disease for uveitis subjects.

The authors report extensive peripheral retinoschisis in a patient with stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) detected by widefield optical coherence tomography (OCT). A 64-year-old woman diagnosed with foveomacular retinoschisis 3 years prior presented for evaluation after being seen by multiple other retina specialists. Standard macular spectral-domain OCT (6 mm) revealed typical foveomacular schisis involving only the outer retina. However, widefield OCT (12 mm) revealed diffuse bilateral retinoschisis involving both inner and outer retinal layers in the macula and midperiphery. Widefield imaging is important to evaluate and monitor complex peripheral retinoschisis that may be otherwise undetectable using conventional techniques. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:774–777.]

BACKGROUND AND OBJECTIVE: Optical coherence tomography angiography (OCTA) is a novel, non-invasive OCT technique capable of imaging the retinal vasculature. This study aims to evaluate the retinal microvasculature in diabetic human subjects with OCTA and assess potential clinical applications. PATIENTS AND METHODS: Cross-sectional study of 33 subjects with diabetic retinopathy. OCTA was performed on 3 mm × 3 mm sections using a swept-source OCTA prototype and a phase- and intensity-based contrasting algorithm. OCT angiograms were studied with corresponding clinical examination and fluorescein angiograms, when available, to assess accuracy and clinical utility. RESULTS: OCTA was able to demonstrate most clinically relevant vascular changes in subjects with diabetic retinopathy, including microaneurysms, impaired vascular perfusion, some forms of intraretinal fluid, vascular loops, intraretinal microvascular abnormalities, neovascularization, and cotton-wool spots that were largely consistent with fluorescein angiography. CONCLUSION: OCTA generates high-resolution angiograms that illustrate many of the clinically relevant findings in diabetic retinopathy and offers a novel complement or alternative to fluorescein angiography. Although currently an investigational technique, OCTA in combination with standard OCT imaging is at least as good as fluorescein angiography in the evaluation of the macular complications of diabetic retinopathy. [ Ophthalmic Surg Lasers Imaging Retina. 2015;46:796–805.]

AimTo evaluate whether people with age-related macular degeneration (AMD) and a history of amblyopia have equal severity of AMD in both eyes.MethodsBilling records were used to locate all people with a history of amblyopia and AMD evaluated between 1 January 2003 and 1 June 2015 at a single ophthalmology institute. Two ophthalmic graders blinded to amblyopia status determined the severity of AMD in each eye using fundus photos and a validated grading scale.ResultsA total of 14 people were found to have AMD and a documented history of amblyopia. Average patient age was 77.0 years and average best corrected visual acuity was 20/160 in eyes with a history of amblyopia and 20/40 in fellow eyes without amblyopia. Eyes with a history of amblyopia were found to have a lower AMD severity score (mean lower score: −1.38; paired t-test P=0.019). Of the 11 people with asymmetric disease severity, 10 individuals had worse AMD in the non-amblyopic eye while one person had worse AMD in the amblyopic eye (P=0.0067).ConclusionsOur pilot study suggests that eyes with a history of amblyopia may manifest decreased severity of AMD compared with non-ambylopic eyes in the same patient. Further research is warranted to investigate this clinical observation.

BACKGROUND AND OBJECTIVE: To noninvasively evaluate the retinal microvasculature in healthy human subjects with optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: Cross-sectional, observational study of five healthy subjects. OCTA was performed on 3 × 3 mm 2 sections centered on the fovea, nasal macula, and temporal macula. Retinal vasculature was assessed within three horizontal slabs consisting of the inner, middle, and outer retina. The vasculature within each retinal slab was reconstructed using phase-based and intensity contrast-based algorithms and visualized as separate en face images. RESULTS: OCTA in healthy subjects demonstrates capillary networks consistent with previous histological studies. No retinal vessels were found in the outer retina. OCT angiography of the inner and middle retinal layers showed region-specific vascular patterns that consistently corroborated qualitative findings from past histological studies. CONCLUSION: OCTA generates high-resolution, noninvasive angiograms qualitatively similar to conventional fluorescein angiography. OCTA may serve as a bridge to assess some features of the retinal microvasculature between conventionally performed angiograms. [ Ophthalmic Surg Lasers Imaging Retina . 2014;45:510–515.]

The diabetic macular edema (DME) treatment paradigm has evolved as the understanding of the disease pathology has grown. Since 2012, four pharmacotherapies have been approved by the U.S. Food and Drug Administration for the treatment of DME. First-line treatment of DME with anti–vascular endothelial growth factor [VEGF] agents has become the gold standard; however, an appreciable percentage of patients do not respond to anti-VEGF therapies. In patients who inadequately respond to anti-VEGF therapies, the underlying disease pathology may be mediated by a multitude of growth factors and inflammatory cytokines. For these patients, corticosteroids are an attractive treatment option because they not only downregulate VEGF, but also an array of cytokines. The phase 3 MEAD and FAME trials demonstrated significant visual acuity improvements associated with dexamethasone and fluocinolone acetonide, respectively, in patients with DME; however, class-specific adverse events, including increased intraocular pressure and cataract development, must be considered before use. A panel of experts gathered during the 2015 annual meeting of the American Academy of Ophthalmology for a roundtable discussion focused on patient selection and adverse event management associated with the use of the 0.19 mg fluocinolone acetonide intravitreal implant. [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:S5–S15.]

PURPOSE: To evaluate the appearance of cuticular drusen with spectral domain optical coherence tomography. METHODS: Eyes of patients with cuticular drusen were imaged using a prototype spectral domain optical coherence tomography instrument with 5-microm axial resolution. Thickness maps were obtained after automated segmentation of the internal limiting membrane and retinal pigment epithelium layers using a proprietary algorithm. The volume of subretinal fluid (SRF) was calculated using a manual segmentation technique that involved drawing boundaries around the SRF. The repeatability of these measurements was tested by comparing the volume measurements from multiple scans performed on the same day in four eyes of three patients. RESULTS: Sixteen eyes from eight patients with cuticular drusen were scanned. Areas of decreased retinal thickness overlying drusen were best visualized using the three-dimensional retinal thickness map. The distribution and sawtooth pattern of cuticular drusen were best visualized using three-dimensional retinal pigment epithelium segmentation. Of the 16 eyes, 13 had SRF within the macula. In the eyes with macular SRF, characteristic excrescences were present along the outer retina and attenuation of the photoreceptor inner and outer segment boundary were observed in many areas. In areas where the retina was detached, the retinal pigment epithelium-Bruch's membrane complex appeared nodular or attenuated. The volumetric measurements of the SRF were performed using a manual segmentation with a 1.11% mean difference between repeated measurements on the same day (range, 0.47-1.68%; standard deviation, 0.55%). CONCLUSION: The sawtooth pattern of drusen and the presence of excrescences along the detached outer retina are characteristic features of cuticular drusen that should be helpful in confirming the diagnosis of this condition. The volumetric analysis of the SRF is repeatable and may be useful in following the clinical course of these patients.

Background and Objective:To compare images of geographic atrophy (GA) obtained using spectral domain optical coherence tomography (SD-OCT) with images obtained using fundus autofluorescence (FAF).Patients and Methods:Five eyes from patients with dry AMD were imaged using SD-OCT and FAF, and the size and shape of the GA were compared.Results:GA appears bright on SD-OCT compared with the surrounding areas with an intact retinal pigment epithelium because of increased reflectivity from the underlying choroid. SD-OCT and FAF both identified GA reproducibly, and measurement of the area of GA is comparable between the two methods with a mean difference of 2.7% of the total area.Conclusion:SD-OCT can identify and quantitate areas of GA. The size and shape of these areas correlate well to the areas of GA seen on autofluorescence images; however, SD-OCT imaging also provides important cross-sectional anatomic information.

An ultra high resolution spectral-domain optical coherence tomography (SD-OCT) together with an advanced animal restraint and positioning system was built for noninvasive non-contact in vivo three-dimensional imaging of rodent models of ocular diseases. The animal positioning system allowed the operator to rapidly locate and switch the areas of interest on the retina. This function together with the capability of precise spatial registration provided by the generated OCT fundus image allows the system to locate and compare the same lesion (retinal tumor in the current study) at different time point throughout the entire course of the disease progression. An algorithm for fully automatic segmentation of the tumor boundaries and calculation of tumor volume was developed. The system and algorithm were successfully applied to monitoring retinal tumor growth quantitatively over time in the LHBETATAG mouse model of retinoblastoma.

Elevation of intraocular pressure (IOP) following injection of intravitreal triamcinolone acetonide (IVTA) is an important clinical problem. The etiology of the steroid response is poorly understood, although a genetic determinant has long been suspected. We performed a pharmacogenomic association study with glucocorticoid receptor polymorphisms.Fifty-two patients (56 eyes) who underwent treatment with IVTA for various retinal diseases were genotyped for six well-studied glucocorticoid receptor polymorphisms (ER22/23EK, N363S, BclI, N766N, and single nucleotide polymorphisms (SNPs) within introns 3 and 4).Three polymorphisms (ER22/23EK, N363S, and the intron 3 SNP) were essentially nonpolymorphic within this population sample and excluded from further analysis. The remaining three polymorphisms (BclI, N766N, and within intron 4) passed the Hardy-Weinberg Equilibrium test, indicating good genotyping quality and normal population distribution of allelic frequency. No statistically significant correlations were found between these three polymorphisms and magnitude of IOP elevation following IVTA, using single point association and haplotype analyses.In this small, pilot study, we found no statistically significant relationship between glucocorticoid receptor polymorphisms and IOP elevation following IVTA. The precise etiology of the steroid response remains obscure. To our knowledge, this is the first published pharmacogenomic study of this common clinical entity.

Background and Objective:A prototype ultrawide field angiographic system and conventional technology were compared.Patients and Methods:Thirty subjects with diabetic retinopathy were imaged in three centers by conventional (Topcon Inc., Paramus, NJ, or Carl Zeiss Meditec, Dublin, CA) and ultrawide field (Optos P200A; Optos Inc., Dunfermline, Scotland) digital fluorescein angiography units. A calibrated grid was digitally placed on the images to facilitate measurements. Main outcome measures were field of view and the number of grid sectors displaying retinal ischemia and neovascularization. Secondary measures were image quality and patient satisfaction scores.Results:The P200A provided a significantly greater visual field extent of 8.7 ± 1.6 disc diameters (DD) compared to the conventional systems (3.4 ± 0.76 DD) (P < .001). Retinal ischemia was better revealed (16.9 ± 15 vs 3.4 ± 4.26 sectors) with the prototype, but image quality was superior with the conventional system. Patient satisfaction scores did not differ between systems.Conclusion:A prototype ultrawide angle imaging system displayed significantly more diabetic retinal pathology in a single image than conventional systems.

Fundus autofluorescence (FAF) has seen a remarkable rise in popularity in recent years. It provides high-contrast gray-scale images of the retinal fundus that carry a degree of cellular metabolic information. In principle, it is based on the excitation of fluorophores within the retinal fundus. The major contributing fluorophore is lipofuscin found in the retinal pigment epithelial (RPE) cells [1].

To noninvasively evaluate the retinal microvasculature in human subjects with retinal venous occlusions using optical coherence tomography angiography and assess potential clinical applications.This was a prospective, observational study of adult human subjects with clinical and imaging findings demonstrating retinal venous occlusion. Subjects underwent complete ophthalmic examination and fluorescein angiography as appropriate for their standard of care. Optical coherence tomography angiography was performed on a prototype spectral domain-OCTA system in 3 mm × 3 mm and 6 mm × 6 mm regions centered on the fovea and parafoveal areas. Retinal vasculature was assessed within three horizontal slabs consisting of the superficial, middle, and deep retina. The vasculature within each slab was reconstructed using intensity contrast-based algorithms and visualized as en-face images. Optical coherence tomography angiograms were manually segmented to verify the accuracy of the automated segmentation algorithms.Optical coherence tomography angiography was able to demonstrate almost all of the clinically relevant findings in 25 subjects with acute and chronic retinal venous occlusion. These findings were consistent with clinical, anatomic, and fluorescein angiographic findings including areas of impaired vascular perfusion, retinal atrophy, vascular dilation, shunt vessels, and some forms of intraretinal edema.Optical coherence tomography angiography is an investigational method that generates high-resolution, noninvasive angiograms that qualitatively illustrate most of clinically relevant findings in retinal venous occlusion. Optical coherence tomography angiography corresponds well with fluorescein angiograms and in many cases provides more detailed anatomic and blood flow information. Optical coherence tomography angiography, in conjunction with standard spectral domain-OCT, is at least equally as effective as fluorescein angiography for evaluation and management of the macular complications of retinal venous occlusions.

Rhodopsin, the light-sensing molecule in the outer segments of rod photoreceptors, is responsible for converting light into neuronal signals in a process known as phototransduction. Rhodopsin is thus a functional biomarker for rod photoreceptors. Here we report a novel technology based on visible-light optical coherence tomography (VIS-OCT) for in vivo molecular imaging of rhodopsin. The depth resolution of OCT allows the visualization of the location where the change of optical absorption occurs and provides a potentially accurate assessment of rhodopsin content by segmentation of the image at the location. Rhodopsin OCT can be used to quantitatively image rhodopsin distribution and thus assess the distribution of functional rod photoreceptors in the retina. Rhodopsin OCT can bring significant impact into ophthalmic clinics by providing a tool for the diagnosis and severity assessment of a variety of retinal conditions.

We developed an optical coherence photoacoustic microscopy (OC-PAM) system, which can accomplish optical coherence tomography (OCT) and photoacoustic microscopy (PAM) simultaneously by using a single pulsed broadband light source. With a center wavelength of 800 nm and a bandwidth of 30 nm, the system is suitable for imaging the retina. Generated from the same group of photons, the OCT and PAM images are intrinsically registered in the lateral directions. To test the capabilities of the system on multimodal ophthalmic imaging, we imaged the retina of pigmented rats. The OCT images showed the retinal structures with quality similar to conventional OCT, while the PAM images revealed the distribution of absorbers in the retina. Since the absorption of hemoglobin is relatively weak at around 800 nm, the NIR PAM signals are generated mainly from melanin in the posterior segment of the eye, thus providing melanin-specific imaging of the retina.

Glaucoma is a leading cause of irreversible blindness, presently affecting approximately 70 million people worldwide.1,2 The most common form is primary open-angle glaucoma (POAG), which accounts for approximately 90% of all cases. Ocular hypertension (OH) is the major risk factor for POAG and lowering IOP is the only effective treatment.3 However, many patients remain refractory to existing IOP-lowering interventions and eventually may become blind, underscoring the unmet medical need for novel approaches to control IOP. Intraocular pressure is a product of the rate of aqueous humor production, resistance to outflow, and episcleral venous pressure.3,4 The aqueous outflow pathways in the angle of the eye are composed of a spongy tissue called the trabecular meshwork (TBM), which leads into Schlemm's canal. Much of the resistance to outflow resides within the TBM, putatively within 7 to 14 μm of the inner wall of Schlemm's canal in a region known as the juxtacanalicular or cribriform region.5–,8 Primary open-angle glaucoma is caused by an increase in outflow resistance9,10 due to poorly understood defects in this region.11–,14 Ocular hypertension in POAG has been associated with dysregulated intracellular signaling pathways controlled by IL-1/NF-κB,15 TGF-β superfamily,16 and Wnt.17,18 The pathophysiology of OH leading to POAG shares many features with a secondary form of OH caused by treatment with glucocorticoids (GCs).19–,25 Glucocorticoids are a class of steroid hormones released in response to stress. As part of the natural feedback mechanism that turns down the inflammatory response, they are useful for treating a wide variety of diseases.26 Complicating this, however, is the considerable interindividual variability and tissue-specific GC sensitivity among individuals, which can cause a variety of systemic side effects.27–,31 Treatment with steroids, such as dexamethasone or triamcinolone acetonide (TA), in the eye causes elevated IOP in predisposed individuals. It has been documented that approximately 40% of the normal population develops an IOP increase > 6 mm Hg above baseline following topical administration of GCs, 4 times a day for 4 to 6 weeks.32 When GCs are administered intravitreally, IOP may increase by 30% or more in up to half of patients.33 These individuals are considered to be “steroid responders.” Interestingly, almost all POAG patients are steroid responders25,32,34–,40; conversely, steroid-responders who do not have POAG are at much higher risk of developing POAG compared to nonresponders.37–,41 A better understanding of genetic and molecular mechanisms underlying individual variation in the response to steroids could shed light on our understanding of steroid-induced OH and OH leading to POAG. That being said, mechanisms of steroid-induced OH and OH leading to POAG also show distinct differences; therefore, studying the genetics of steroid-induced OH specifically could lead to discovery of genes involved in IOP regulation that could not have been revealed any other way. The genome-wide association study (GWAS) represents an agnostic approach for prioritization of genes that are associated with a disease process, and makes it possible to discover novel genes that could not otherwise be identified. In the current study, we performed a pharmaco-GWAS for this purpose, using a cohort enrolled from patients treated with off-label intravitreal TA (IVTA) for various retinal indications, and followed up with an independent candidate gene study. We identified two independent quantitative trait loci (QTLs) at chromosomal locus 6p21.33 associated with the novel mucin gene HCG22.

PURPOSE To evaluate the safety and efficacy of intravitreal bevacizumab (Avastin, Genentech Inc.) for the treatment of neovascular age-related macular degeneration (ARMD). METHODS A retrospective review was performed on consented patients with neovascular ARMD receiving intravitreal bevacizumab therapy. All patients received intravitreal bevacizumab at baseline with additional monthly injections given at the discretion of the treating physician. At each visit, a routine Snellen visual acuity assessment was performed followed by an ophthalmic examination and optical coherence tomography (OCT) imaging. RESULTS Fifty-three eyes of 50 patients received an intravitreal bevacizumab injection between May and August 2005. Including the month 3 visit, the average number of injections was 2.3 out of a maximum of 4 injections. No serious drug-related ocular or systemic adverse events were identified. Improvements in visual acuity and central retinal thickness measurements were evident by week 1 and continued through month 3. At month 3, the mean visual acuity improved from 20/160 to 20/125 (P < 0.001) and the mean central retinal thickness decreased by 99.6 microm (P < 0.001). CONCLUSION Off-label intravitreal bevacizumab therapy for neovascular ARMD was well tolerated over 3 months with improvements in visual acuity and OCT central retinal thickness measurements. While the long-term safety and efficacy of intravitreal bevacizumab remain unknown, these short-term results suggest that intravitreal bevacizumab may be the most cost effective therapy for the treatment of neovascular ARMD.

To determine whether intravitreal bevacizumab could improve optical coherence tomography and visual acuity outcomes in a patient with neovascular age-related macular degeneration who was responding poorly to pegaptanib therapy, an intravitreal injection of bevacizumab (1.0 mg) was given. Within 1 week, optical coherence tomography revealed resolution of the subretinal fluid, resulting in a normal-appearing macular contour. The improved macular appearance was maintained for at least 4 weeks, and visual acuity remained stable. No inflammation was observed. An intravitreal injection of bevacizumab may provide an effective, safe, and inexpensive option for patients with age-related macular degeneration who are losing vision secondary to macular neovascularization. [Ophthalmic Surg Lasers Imaging 2005;36:331-335.]

To determine whether bevacizumab could improve visual acuity and optical coherence tomography outcomes in a patient with macular edema from central retinal vein occlusion, an intravitreal injection of bevacizumab (1.0 mg) was given. Prior intravitreal injections of triamcinolone acetonide resulted in vision improvement but worsening cataract and borderline glaucoma. Wthin 1 week of the bevacizumab injection, visual acuity improved from 20/200 to 20/50 and optical coherence tomography revealed resolution of the cystic maculopathy. The improvements were maintained for at least 4 weeks. Intravitreal injections of bevacizumab may provide another treatment option for patients with macular edema from vein occlusions. [Ophthalmic Surg Lasers Imaging 2005;36:336-339.]

This article reviews pegaptanib sodium, a compound developed by Eyetech Pharmaceuticals Inc. and Pfizer Inc., for the treatment of neovascular age-related macular degeneration (AMD). Traditional treatment approaches to neovascular AMD have included destructive therapies such as thermal laser photocoagulation and photodynamic therapy; the use of pegaptanib sodium heralds a new treatment approach that is a non-destructive therapy based on the inhibition of vascular endothelial growth factor activity in the eye. This diminishes the neovascular drive in the pathologically hyperpermeable state of the diseased eye. Pegaptanib sodium is one of the first therapeutics belonging to the class of compounds known as aptamers. The chemistry, mechanism of action, pharmacokinetics and rationale for the clinical use of the drug are reviewed. The article highlights and summarises the results of the multi-centre, randomised, sham-controlled clinical trials with pegaptanib sodium to treat subfoveal choroidal neovascularisation in AMD. In addition, the safety profile is reviewed.

Purpose To report clinical and optical coherence tomography (OCT) features in patients with idiopathic macular hole and extensive subretinal fluid (extending at least 1 disk diameter from the center of the hole). Design Retrospective, consecutive, noncomparative case series. Methods The case records of two patients with idiopathic macular holes with extensive subretinal fluid were reviewed. Results Both patients presented with reduced visual acuity (20/200 and 20/400). OCT demonstrated attachment of the posterior hyaloid to the inner retina, a full-thickness macular hole, cystoid macular edema (CME), and extensive subretinal fluid. After surgery, both patients achieved macular hole closure and improvement in visual acuity (20/60 and 20/30). Postoperatively, OCT showed a normal foveal contour, complete hole closure, and resolution of the CME and subretinal fluid. Conclusions In patients with macular hole and extensive subretinal fluid, improved visual acuity and hole closure can be achieved. Preoperative OCT in these patients demonstrates vitreoretinal interface abnormalities, CME, and extensive subretinal fluid. These changes resolve postoperatively.

Polypoidal choroidal vasculopathy is an abnormality of the choroidal vasculature characterized by aneurysmal-like budding of the vessels with exudation and recurrent serosanguinous detachments of the retinal pigment epithelium. Treatment is limited to laser photocoagulation of leaking vessels, which is used when vision is decreased, or exudate and hemorrhage threaten or involve the fovea. This article describes a patient with polypoidal choroidal vasculopathy successfully treated with photodynamic therapy using verteporfin. [Ophthalmic Surg Lasers Imaging 2003; 34:60-63]

PURPOSE: To develop an optical coherence tomography (OCT) classification system that monitors the response of eyes treated with photodynamic therapy (PDT) with verteporfin for subfoveal choroidal neovascularization (CNV) from age-related macular degeneration (AMD). DESIGN: Retrospective interventional case series. METHODS: Ninety eyes (88 patients) with AMD and predominantly classic subfoveal CNV treated with PDT using verteporfin were identified by a laser log and retrospectively reviewed. Optical coherence tomography and fluorescein angiography (FA) were performed before treatment and at subsequent follow-up examinations in all eyes. Optical coherence tomography findings were evaluated and compared with corresponding FA. RESULTS: A five-stage OCT classification of eyes treated with PDT was created from the evaluation of 79 total eyes (77 patients). Stage I (two eyes) is recognized within the first week of treatment and demonstrates an acute inflammatory response with increased subretinal fluid. Stage II (28 eyes) represents the restoration of a near-normal fovea contour with diminished subretinal fluid occurring 1 to 4 weeks after treatment. Stage III (79 eyes) occurs between 4 to 12 weeks following treatment and is subdivided into two categories based on the amount of subretinal fibrosis and fluid present. Stage IIIa (15 eyes) contains a greater subretinal fluid to fibrosis ratio indicating an active CNV process. Lesions in stage IIIb (64 eyes) less actively leak and have more prominent fibrosis with minimal intraretinal fluid. Cystoid macular edema defines a stage IV lesion (11 eyes). In stage V lesions (19 eyes) the subretinal fluid resolves with thinning of the retina as well as fibrosis merging with the retinal pigment epithelial layer (RPE). CONCLUSION: Optical coherence tomography appears to be useful in monitoring the retinal changes that occur following PDT of CNV and may assist in understanding the changes observed on angiography.

Purpose To quantitatively evaluate the retinal microvasculature in human subjects with retinal venous occlusions (RVO) using optical coherence tomography angiography (OCTA). Design Retrospective, cross-sectional, observational case series. Participants Sixty subjects (84 eyes) were included (20 BRVO, 14 CRVO, 24 unaffected fellow eyes, and 26 controls). Methods OCTA was performed on a prototype, spectral domain-OCTA system in the 3x3mm central macular region. Custom software was used to quantify morphology and density of retinal capillaries using four quantitative parameters. The vasculature of the segmented retinal layers and nonsegmented whole retina were analyzed. Main outcome measures Fractal dimension (FD), vessel density (VD), skeletal density (SD), and vessel diameter index (VDI) within the segmented retinal layers and nonsegmented whole retina vasculature. Results Nonsegmented analysis of RVO eyes demonstrated significantly lower FD (1.64±0.01 vs 1.715±0.002; p

This editorial outlines the development of optical coherence tomography (OCT) technology and discusses the emergence of OCT angiography as a true extension of capabilities from spectral-domain OCT.

Purpose. To evaluate the efficacy of transpupillary thermotherapy (TTT) for the treatment of occult choroidal neovascularization. Methods. A retrospective, noncomparative case series of 57 eyes of 52 patients who presented with occult subfoveal CNV and were treated with TTT. Results. 83% of eyes were either stable (+/− one line) or showed improvement in visual acuity. 83% of eyes showed stabilization of their exudative process after one TTT treatment as evidenced by resorption of subretinal and/or intraretinal exudate or hemorrhage. Nine percent of eyes developed classic CNV during the mean follow-up time of ten months. Conclusions. TTT appears to stabilize the exudative process in eyes with occult CNV. A prospective, sham-controlled, randomized study (TTT4CNV Clinical Trial) is currently underway to directly compare TTT to the natural history of occult CNV

* BACKGROUND AND OBJECTIVE: To demonstrate the utility of optical coherence tomography (OCT) for documenting an early response to laser photocoagulation in clinically significant macular edema (CSME) secondary to diabetes. * PATIENTS AND METHODS: Five eyes of four patients were selected for review based on the diagnosis of CSME. All eyes had a clinical diagnosis of CSME based on slit lamp bíomicroscopy. All eyes underwent focal/grid laser photocoagulation to areas of retinal thickening detected by OCT and clinical exam. Pre and post-treatment optical coherence tomograms were obtained for all patients. * RESULTS: All eyes selected for review had an early positive response to focal laser photocoagulation. OCT was useful for demonstrating areas of retinal thickening prior to laser treatment. Serial macular maps demonstrated the resolution of retinal thickening after laser photocoagulation in all eyes. * CONCLUSION: OCT is a useful tool for evaluating and documenting CSME both before and after focal/grid laser photocoagulation. OCT is capable of detecting an early positive response to photocoagulation for macular edema. [Ophthalmic Surg Lasers 2000;31:192-197]

Ophthalmologists, with respect to both therapeutic and diagnostic applications, have traditionally been at the forefront of laser technology. The proliferation of new technologies and the ingenious application of these technologies over the last several decades ensures that ophthalmologists will continue to be at the vanguard of laser technology well into the next millennium. This article reviews both past and present applications of laser technology and provides an overview of future developments in laser technology within the field of ophthalmology. The history of lasers dates to 1960, when the first functioning laser was demonstrated by Maiman. 76 It was not until 1963 and 1964 when Campbell 19 and Zweng, 141 respectively, reported the first clinical ophthalmic use of a laser in humans, however. They employed a pulsed ruby laser for retinal photocoagulation. They found that laser photocoagulation was efficient, effective, and did not require anesthesia or akinesia. They found that the use of a pulsed laser led to the formation of retinal hemorrhages and had difficulty producing full-thickness retinal burns; this led to the development of continuous wave, gas ion lasers. In 1964, the argon laser, which provides an emission spectrum that is well absorbed by hemoglobin and is used in a continuous mode, was developed. L'Esperance conducted the first human photocoagulation trial for ophthalmic disease using the argon laser in 1968 69 ; he also introduced the frequency-doubled neodymium:yttrium-aluminum-garnet (Nd:YAG) and krypton lasers in 1971 and 1972, respectively. The use of Q-switched and mode-locked Nd:YAG lasers in 1980 and 1981, respectively, provided the ability to produce short bursts of energy that allowed transparent membranes (vitreous, posterior capsules) to be cut. The tunable dye laser was introduced in 1981 and provided the theoretical advantage of a variable output wavelength to match the absorption spectra of specific ocular tissue. The semiconductor infrared diode laser was developed in 1962. Since then, the diode laser has been employed in multiple delivery modes: transpupillary slit lamp, transpupillary laser indirect, transcleral, and endophotocoagulation. It has proven useful in the treatment of choroidal neovascularization, proliferative diabetic retinopathy, retinopathy of prematurity, macular edema, and choroidal melanoma. 84,103 The midinfrared CO 2 laser was developed in 1964 and has been used to perform corneal ablations. 102 This application has been limited by tissue shrinkage and thermal damage to surrounding tissue. 57 In the 1980s, the CO 2 laser was used in skin resurfacing and is now a common technique of rhytid and scar removal. More recently, the CO 2 laser has been used to perform soft-tissue incisional surgery, such as for incisional blepharoplasty. A variety of excimer lasers have been developed. These lasers are capable of emitting pulses of 10 ns and the active medium consists of an excited rare-gas atom with a halogen molecule, resulting in an excited dimer, or excimer. 18 The initial use of the excimer laser, in the early 1980s, was to precisely etch submicrometer patterns into polymer materials for use in the semiconductor industry. 31,61 Srinivasan 120 has termed this controlled removal of material, in which molecules on the irradiated surface are broken into small volatile fragments, ablative photodecomposition. The first ophthalmic use of the excimer laser was reported in 1983 by Trokel, who used the excimer laser to achieve precise etching of the cornea. 130 Since then, a wealth of activity has centered on corneal ablation by the excimer laser, leading to the current interest in laser refractive surgery. A host of new lasers, such as the erbium:YAG (Er:YAG), Q-switched 532 nm Nd:YAG and holmium:YAG lasers promise either improvements in current techniques or novel applications. These new laser techniques may widen the indications for refractive surgery, improve outcomes in glaucoma surgery, obviate the need for vitroretinal surgery in some cases, improve outcomes in oculoplastic procedures, and even help to remove cataracts. Table 1 describes these new ophthalmic lasers and their associated features. Table 2 lists novel applications of existing laser technology.

Objective To evaluate the efficacy of transpupillary thermotherapy for the treatment of occult subfoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration. Design A retrospective, noncomparative case series. Participants Sixteen eyes of 15 consecutive patients who presented with occult subfoveal choroidal neovascularization secondary to age-related macular degeneration. Intervention After informed consent was obtained, 16 eyes of 15 patients were treated with transpupillary thermotherapy. All patients underwent pretreatment fluorescein angiography and were deemed untreatable by the Macular Photocoagulation Study standard. Transpupillary thermotherapy was delivered using a diode laser at 810 nm. A variable spot size of 1.2 mm, 2.0 mm, or 3.0 mm was used depending on the size of CNV. The diode laser was delivered through a contact lens, and treatment was initiated in one spot for 60 seconds’ duration at a power range between 360 and 1000 mW. The end point was an area of no visible color change to a light-gray appearance. Main outcome measures In all eyes, outcome was assessed by Snellen chart visual acuity and clinical examination. In 10 of 16 eyes, preoperative and postoperative fluorescein angiography and optical coherence tomography were available. In the remaining 6 of 16 eyes, exudation was measured by postoperative clinical examination alone. Results Three eyes (19%) showed a two-or-more-line improvement in visual acuity over a period of 6 to 25 months. Mean follow-up was 13 months. Visual acuity remained stable (no change or one-line improvement) in nine treated eyes (56%). The remaining four eyes (25%) showed a decline (equal to one-line worsening or greater) in visual acuity. Fifteen eyes (94%) demonstrated decreased exudation on fluorescein angiography, optical coherence tomography, and/or clinical examination. Conclusions Transpupillary thermotherapy shows no deleterious side effects in treating occult subfoveal choroidal neovascularization. A randomized, prospective study is necessary to evaluate treatment efficacy.

To analyze glaucomatous eyes with known focal defects of the nerve fiber layer (NFL), relating optical coherence tomography (OCT) findings to clinical examination, NFL and stereoscopic optic nerve head (ONH) photography, and Humphrey 24-2 visual fields.Cross-sectional prevalence study.The authors followed 19 patients in the study group and 14 patients in the control group.Imaging with OCT was performed circumferentially around the ONH with a circle diameter of 3.4 mm using an internal fixation technique. One hundred OCT scan points taken within 2.5 seconds were analyzed.Measurements of NFL thickness using OCT were performed.In most eyes with focal NFL defects, OCTs showed significant thinning of the NFL in areas closely corresponding to focal defects visible on clinical examination, to red-free photographs, and to defects on the Humphrey visual fields. Optical coherence tomography enabled the detection of focal defects in the NFL with a sensitivity of 65% and a specificity of 81%.Analysis of NFL thickness in eyes with focal defects showed good structural and functional correlation with clinical parameters. Optical coherence tomography contributes to the identification of focal defects in the NFL that occur in early stages of glaucoma.

Objective To assess the potential of optical coherence tomography (OCT) to differentiate retinoschisis from retinal detachment. Optical coherence tomography is a noninvasive, noncontact imaging method that produces high-resolution, cross-sectional images of ocular tissue. Design Retrospective case series. Participants Thirteen eyes of 12 patients with the differential diagnosis of retinoschisis versus retinal detachment. Methods Differentiation between retinoschisis and retinal detachment was established from both ophthalmoscopic and OCT examinations. Main outcome measure Ability of OCT to differentiate retinoschisis from retinal detachment was measured. Results Thirteen eyes of 12 patients with retinal elevation were examined with OCT. The cross-sectional view produced by OCT was effective in distinguishing retinoschisis from retinal detachment. Optical coherence tomography images of retinoschisis show a splitting of the neurosensory retina. The OCT images of retinal detachment show separation of full-thickness neurosensory retina from the retinal pigment epithelium band. The OCT images correlated with the clinical impression in all 13 cases. Conclusions Based on this series of cases, OCT is a potentially useful new test that may be used to distinguish retinoschisis from rhegmatogenous retinal detachment.

A prototype 6-μm axial resolution spectral domain optical coherence tomography (SD-OCT) device was used to image the retina of a patient with uncontrolled diabetes mellitus who had proliferative diabetic retinopathy with subhyaloid hemorrhage. A raster scan pattern with 128 B-scans covering a 6 × 6 × 2-mm volume of the retina was obtained. SD-OCT showed the presence of blood localized between the internal limiting membrane and the posterior hyaloid face and allowed visualization of the cross sectional retinal architecture and the vitreoretinal interface at different horizontal levels that could be registered with the color fundus photograph. SD-OCT provided useful information about the relationship of the hemorrhage to the posterior hyaloid and the retina.

The authors report using spectral domain optical coherence tomography (OCT) to observe a patient with an optic nerve pit and macular schisis-like spaces. An 8-µm axial resolution prototype spectral domain OCT and stereo fundus photography were used to observe the patient. A macular schisis-like cavity was present at baseline and additional cystic changes developed in the nerve fiber layer over a period of 16 months; however, the visual acuity remained stable at 20/20. Spectral domain OCT provides greater detail of the changes in morphology and structure of macular schisis and edema associated with an optic nerve pit. [Ophthalmic Surg Lasers Imaging 2007;38:262-264.] AUTHORS From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida. Accepted for publication December 12, 2006.Supported in part by Research to Prevent Blindness, Inc., New York, New York. Research funding provided in part by a grant from Carl Zeiss Meditec (OSP, GAL, RWK, CAP). Dr. Puliafito is a Research and Clinical Consultant for Carl Zeiss Meditec.Dr. Puliafito did not participate in the editorial review of this manuscript.Address correspondence to Geeta A. Lalwani, MD, 900 NW 17th Street, Miami, FL 33136.

Objective: This study aimed to develop a protocol to screen and monitor patients with diabetic macular thickening using optical coherence tomography (OCT), a technique for high-resolution cross-sectional imaging of the retina. Design: A cross-sectional pilot study was conducted. Participants: A total of 182 eyes of 107 patients with diabetic retinopathy, 55 eyes from 31 patients with diabetes but no ophthalmoscopic evidence of retinopathy, and 73 eyes from 41 healthy volunteers were studied. Intervention: Six optical coherence tomograms were obtained in a radial spoke pattern centered on the fovea. Retinal thickness was computed automatically from each tomogram at a total of 600 locations throughout the macula. Macular thickness was displayed geographically as a false-color topographic map and was reported numerically as averages in each of nine regions. Main Outcome Measures: Correlation of OCT with slit-lamp biomicroscopy, fluorescein angiography, and visual acuity was measured. Results: Optical coherence tomography was able to quantify the development and resolution of both foveal and extrafoveal macular thickening. The mean ± standard deviation foveal thickness was 174 ± 18 μ m in normal eyes, 179 ± 17 μ m in diabetic eyes without retinopathy, and 256 ± 114 μ m in eyes with nonproliferative diabetic retinopathy. Foveal thickness was highly correlated among left and right eyes of normal eyes (mean ± standard deviation difference of 6 ± 9 μ m). Foveal thickness measured by OCT correlated with visual acuity ( r 2 = 0.79). A single diabetic eye with no slit-lamp evidence of retinopathy showed abnormal foveal thickening on OCT. Conclusions: Optical coherence tomography was a useful technique for quantifying macular thickness in patients with diabetic macular edema. The topographic mapping protocol provided geographic information on macular thickness that was intuitive and objective.

Sustained-release ganciclovir implants are effective in delaying progression of newly diagnosed cytomegalovirus (CMV) retinitis. An uncontrolled case series was assembled to evaluate the efficacy of the intravitreal ganciclovir implant for patients with sight-threatening CMV retinitis who had previously failed to respond to intravenous ganciclovir and/or foscarnet.Between August 1993 and March 1995, 72 eyes of 55 patients received intravitreal ganciclovir implants. Patients were examined monthly after implant surgery.A total of 56 eyes (77.8%) were available for evaluation after implant surgery. At the 1-month postoperative visit, 48 eyes (85.7%) of 38 patients had no progression. Implants failed to control progression at the 1-month visit in eight eyes (14.3%) of six patients receiving primary implants. A total of 32 eyes (57.1%) of 29 patients did not experience three-line loss of visual acuity through the follow-up period. The median time to three-line loss was 190 days from implantation. Four eyes (7.1%) developed visual acuity of 20/200 or worse by the 1-month follow up. The median time from implantation to development of visual acuity of 20/200 or less was 224 days. The median survival time was 376 days from study entry. The most common postoperative complication was retinal detachment, which was observed in 12 eyes receiving implants. Additional self-limiting complications included significant vitreous hemorrhage (three eyes) and hypotony maculopathy (two eyes).Ganciclovir implants were effective in delaying visual loss in a significant proportion of patients who failed ganciclovir or foscarnet therapy. A number of these patients, however, experienced visual loss. Although the implants can be effective as therapy for relapsed CMV retinitis, the efficacy does not appear to match that noted in initial CMV retinitis therapy.

Objective: The purpose of the study is to define qualitative patterns of corneal topography after excimer laser photorefractive keratectomy (PRK) using a 6-mm beam diameter, investigate changes in patterns over time, and identify associations of topography patterns with clinical outcomes. Design: Multicenter, prospective cohort study. Participants: Ninety-eight eyes of 90 patients with myopia who had undergone PRK using the Summit Technology, Inc., excimer laser with a 6-mm beam diameter. Intervention: Computer-assisted videokeratography data were analyzed for eyes having undergone PRK. Topography patterns at 3, 6, and 12 months after surgery were classified and associations with clinical outcomes assessed. Main Outcomes Measured: Topography patterns after PRK were determined at 3, 6, and 12 months after surgery. Associations with preoperative characteristics of age and attempted correction, and postoperative outcomes of uncorrected and spectacle-corrected visual acuity, predictability, astigmatism, corneal haze, glare, halo, and patient satisfaction were analyzed. Results: At 1 year, 21.4% of corneas showed a homogeneous topography, 27.6% showed a toric-with-axis configuration, 10.2% showed a toric-against-axis configuration, 7.1% showed an irregularly irregular topography, 24.5% showed a keyhole/semicircular pattern, and 9.2% showed focal topographic variants. From 3 to 6 months, 40.1 % of maps changed; from 6 to 12 months, 53.1 % of maps changed, generally to optically smoother, regular patterns. Older age and higher attempted correction were associated with the development of more irregular patterns. The irregular groups showed worse predictability than did the regular groups and a tendency for slight overcorrection. The average reported glare/halo of 1.33 (scale = 0 to 5) in this study was less than in a previous study of the 4.5- to 5-mm treatment zone. However, of six patients expressing dissatisfaction with the results of surgery, three ranked their glare or halo at the maximum level. Conclusions: Topography patterns using a 6-mm beam diameter are identifiable, improve with time, and may affect clinical outcomes after photorefractive keratectomy (PRK). The keyhole/semicircular pattern is more prevalent with a 6 mm treatment zone than with smaller treatment zones. Although optical side effects of glare and halo appear to be reduced with the 6-mm treatment, a small number of patients still report substantial glare or halo after the procedure.

Purpose: The authors determine if specific features of the clinical presentation of acute postoperative endophthalmitis correlate with the microbiologic culture results. Methods: A total of 420 patients who had clinical evidence of endophthalmitis within 6 weeks after cataract surgery or secondary intraocular lens implantation were evaluated as part of a randomized clinical trial. Results of cultures performed on aqueous and vitreous specimens obtained at presentation were categorized as follows: gram-positive coagulase-negative micrococci, "other" gram-positive, gram-negative, and equivocal/no growth. Results: Eleven features of the initial clinical presentation were associated with significant differences in the microbiologic spectrum ( P Conclusions: The presenting characteristics of acute endophthalmitis after cataract surgery may be helpful in predicting the most likely culture results. Such predictions do not appear sufficiently strong to guide the initial empiric choice of intravitreal antibiotics.

Optical coherence tomography (OCT) has developed rapidly since its first realisation in medicine and is currently an emerging technology in the diagnosis of skin disease. OCT is an interferometric technique that detects reflected and backscattered light from tissue and is often described as the optical analogue to ultrasound. The inherent safety of the technology allows for in vivo use of OCT in patients. The main strength of OCT is the depth resolution. In dermatology, most OCT research has turned on non-melanoma skin cancer (NMSC) and non-invasive monitoring of morphological changes in a number of skin diseases based on pattern recognition, and studies have found good agreement between OCT images and histopathological architecture. OCT has shown high accuracy in distinguishing lesions from normal skin, which is of great importance in identifying tumour borders or residual neoplastic tissue after therapy. The OCT images provide an advantageous combination of resolution and penetration depth, but specific studies of diagnostic sensitivity and specificity in dermatology are sparse. In order to improve OCT image quality and expand the potential of OCT, technical developments are necessary. It is suggested that the technology will be of particular interest to the routine follow-up of patients undergoing non-invasive therapy of malignant or premalignant keratinocyte tumours. It is speculated that the continued technological development can propel the method to a greater level of dermatological use.

This editorial describes the challenge of managing eyes that demonstrate signs of persistent exudation after anti-VEGF treatment and illuminates the significance of a new report of using high-dose ranibizumab in treating recalcitrant neovascular age-related macular degeneration.