Qualitative and quantitative OCT response of diffuse diabetic macular oedema to macular laser photocoagulation

Purpose

To assess the quantitative and morphological changes of the macula in response to macular grid laser for diabetic macular oedema (DMO) using optical coherence tomography (OCT).

Patients and Methods

Cirrus OCT macular cube scans of 30 eyes of 25 patients were retrospectively analysed before and 4 months after macular grid laser for diffuse DMO. The oedema was quantified and response evaluated in the nine early-treatment diabetic retinopathy study (ETDRS) zones of the macula. Post-laser OCT changes were compared with the baseline features, including morphology patterns, changes in both logarithmic transformed (logOCT) and standardised average macular thickness (AMT), total macular volume, number of parafoveal quadrants involved, and the presence of intact 3rd hyper-reflective band (HRB).

Results

The rate of change of retinal thickness in response to laser was maximum in the central (8.17%) and perifoveal inferior quadrants (0.04%). Diffuse retinal thickening on OCT responded best to treatment. The AMT of 300–350 μm had the worst response (+0.94%). Eyes with less than four quadrants of oedema showed good response. Disrupted HRB was associated with poor visual gain (−0.33 ETDRS letters).

Conclusion

The topographic location of oedema on the retinal map and the morphological patterns of the oedema on OCT are useful predictors of treatment response in diffuse DMO.     

Spectral- and time-domain optical coherence tomography measurements of macular thickness in normal eyes and in eyes with diabetic macular edema

Purpose

To report macular thickness values in normal eyes and eyes with diabetic macular edema (DME) using time-domain (TD) and spectral-domain (SD) optical coherence tomography (OCT), and to derive a conversion equation.

Methods

The index study was a prospective investigation conducted on 80 eyes from 40 normal subjects and 130 eyes from 118 patients with DME seen in our clinic. Retinal thickness values from the central 1 mm of the macula and surrounding four ETDRS subfields were acquired using TD-OCT (Stratus OCT) and SD-OCT (SPECTRALIS HRA+OCT). Measurements of the central (C) subfield from both devices were used to derive a conversion equation. The equation was used to predict SD-OCT values using measurements from TD-OCT. Agreement between predicted and actual SD-OCT measurements was assessed.

Results

In normal eyes, the mean difference between TD-OCT and SD-OCT measurements of the C subfield was 76 μm (CI₉₅=74 and 77, respectively). The conversion equation, y=1.029x+72.49, was derived. In eyes with DME, using the equation, SPECTRALIS-predicted values were 5% higher than actual measurements, with 95% of predicted values falling within 9% of the actual measurements. Relocating SD-OCT grids to match the location on TD-OCT resulted in predicted values falling within 7% of actual measurements.

Conclusions

The percent difference between actual thickness measurements from SPECTRALIS and predicted thickness measurements, using the conversion equation, was within reported limits of repeatability of Stratus in eyes with DME. Our equation may help correlate OCT values from both devices in standard care and clinical trials for DME.     

Ranibizumab for the treatment of choroidal neovascularisation secondary to pathological myopia: interim analysis of the REPAIR study

Aims

To evaluate the efficacy and safety of intravitreal ranibizumab in patients with choroidal neovascularisation secondary to pathological myopia (myopic CNV). Data are from a pre-planned, 6-month interim analysis.

Methods

Phase II, open-label, single arm, multicentre, 12-month study, recruiting patients (aged ≥18 years) with active primary or recurrent subfoveal or juxtafoveal myopic CNV, with a best-corrected visual acuity (BCVA) score of 24–78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the study eye and a diagnosis of high myopia of at least −6 dioptres.Patients received 0.5 mg ranibizumab administered intravitreally to the study eye, followed by monthly injections given as needed (based on a predefined algorithm) for up to 11 months.

Results

At 6 months, mean BCVA improved from baseline by 12.2 letters, as did central macular thickness (in this interim analysis defined as a measure of either central subfield macular thickness or centre point macular thickness) from baseline by 108 μm in the 48 study eyes of 48 patients. Fewer patients had centre-involving intraretinal oedema (13.0% vs 91.5%), intraretinal cysts (10.9% vs 57.4%), or subretinal fluid (13.0% vs 66.0%) at 6 months than at baseline. Patients received a mean of 1.9 retreatments, were satisfied with ranibizumab treatment, and well being was maintained. No new safety signals were identified.

Conclusions

Results from the planned interim analysis support the role of ranibizumab in the treatment of myopic CNV, with excellent efficacy achieved with a low number of injections and few serious adverse events.     

Choroidal thickness in both eyes of patients with unilaterally active central serous chorioretinopathy

Objective

To assess the change in the choroidal thickness of the unaffected eyes in patients with unilateral central serous chorioretinopathy (CSC).

Methods

Thirty eyes with unilateral idiopathic CSC and 30 age-matched normal eyes were included in this study. Choroidal thickness was evaluated from images obtained by enhanced depth image optical coherence tomography. The choroidal thicknesses of the affected eyes, unaffected eyes, and normal eyes were analyzed. Choroidal vascular dilation and hyperpermeability on indocyanine green angiography (ICGA) were analyzed and correlated with the changes in choroidal thickness.

Results

The mean choroidal thicknesses of the affected eyes, unaffected fellow eyes, and normal individuals were 445.58±100.25, 378.35±117.44, and 266.80±55.45 μm, respectively. Compared with normal eyes, subfoveal choroidal thickness was increased significantly in the eyes with active CSC and in the unaffected fellow eyes (P<0.001 in both groups). The choroidal thickness was significantly greater in the eyes with active CSC than in the unaffected fellow eyes (P=0.003). ICGA revealed choroidal vascular hyperpermeability in 28 (93.3%) eyes with CSC and in 23 (73.3%) unaffected fellow eyes. Choroidal vascular dilation was detected in 21 (70.0%) eyes with CSC and in 18 (60.0%) unaffected fellow eyes.

Conclusion

Increased choroidal thickness in patients with unilateral CSC was noted not only in the affected eyes, but also in the unaffected fellow eyes. The results of this study suggest that CSC might be an essentially bilateral disorder.     

Retinal vascular changes following intravitreal ranibizumab injections for neovascular AMD over a 1-year period

Purpose

To assess retinal vascular calibre changes in eyes with neovascular age-related macular degeneration (AMD), treated with intravitreal anti-vascular endothelial growth factor agents, over a 1-year period and compare any such changes to untreated fellow eyes.

Methods

Treatment naïve patients with neovascular AMD received three consecutive intravitreal injections of ranibizumab, followed by a pro re nata dosing regimen up to 1 year, with the aim of maintaining a ‘fluid-free'' macula. Retinal arteriolar and venular calibre was measured from digital fundus photographs at baseline and at three monthly intervals to 1 year, and summarised as central retinal artery equivalent (CRAE) and central retinal venular equivalent (CRVE), respectively.

Results

A total of 53 injected eyes and 41 fellow, non-injected eyes were analysed. At baseline, there were no differences in retinal vascular calibre between injected and non-injected eyes (mean CRAE (SD) 144.93 (14.07) vs 145.74 (13.10) μm, P=0.80 and mean CRVE (SD) 216.23 (25.93) vs 219.91 (22.82) μm, P=0.53). Over a 12-month period, retinal venular calibre dilatation occurred in injected eyes (mean CRVE change +5.71 (14.71) μm, P=0.007), with no change in retinal arterioles, +0.69 (14.71) μm, P=0.68. In non-injected eyes, arteriolar narrowing occurred as a whole, mean CRAE change −4.20 (7.00) μm, P=0.001, over 12 months, with a trend for narrowing in venules, −2.16 (11.56) μm, P=0.28. In injected eyes, after controlling for covariates, the changes in CRVE over 12 months mirrored improvements in macular thickness, −0.06 (−0.005, −0.11) μm, P=0.04, and visual acuity, +9.66 (−0.30, +19.32) μm, P=0.06.

Conclusion

Intravitreal ranibizumab significantly dilated retinal venules after a 1-year period.     

Comparison of retinal thickness values and segmentation performance of different OCT devices in acute branch retinal vein occlusion

Purpose

To compare retinal thickness (RT) measurement and segmentation performance of time domain (TD, Stratus) and spectral domain (SD) optical coherence tomography (OCT) devices (Cirrus, Spectralis) for imaging macular oedema (ME) secondary to branch retinal vein occlusion (BRVO).

Methods

In this study, 20 eyes of 20 consecutive patients with acute BRVO were included. A total of 18 unaffected fellow eyes served as control group. RT measurement was analysed in the five inner fields of the early-treatment diabetic retinopathy grid, and proportional segmentation errors were evaluated.

Results

Central millimetre thickness (CMT) showed a mean difference of −64, −74, and −18 μm (P<0.001) in the control group and −31 μm (P=0.107), −92 μm (P<0.001), and −105 μm (P=0.016) in the BRVO group, between Stratus and Cirrus, between Stratus and Spectralis, and between Cirrus and Spectralis, respectively. Mean RT showed the highest variability between different devices in the area most intensively affected by BRVO-related ME. In eyes with BRVO, 14.6% of Spectralis, 20% of Stratus, and 36.6% of Cirrus scans demonstrated moderate and severe segmentation errors.

Conclusion

RT measurement in eyes with BRVO, by TD and SD OCT, is compromised by a significant rate of segmentation errors. Deviations are most pronounced in the areas most severely affected by ME.     

Longitudinal comparison of visual acuity as measured by the ETDRS chart and by the potential acuity meter in eyes with macular edema,and its relationship with retinal thickness and sensitivity

Purpose

To evaluate the relationship between visual acuity as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart and by the potential acuity meter (PAM) with retinal thickness and sensitivity measured by a combined microperimetry/optical coherence tomography system (OCT).

Methods

Forty-four patients with macular edema (ME) were included in a prospective observational study. Visual acuity (VA) was assessed using the ETDRS chart (with best correction) as well as by the PAM. Retinal thickness and sensitivity was measured by an automatic fundus perimetry/tomography system.

Results

Best-corrected VA using the ETDRS chart ranged from 20/20 to 20/400 (median: 20/50). VA measured by the PAM without correction ranged from 20/20 to 20/400 (median: 20/40). The mean retinal thickness was 369.57 μm (s.d.: 140.28 μm) on spectral domain-OCT and the mean retinal sensitivity was 8.12 decibels (dB) (s.d.: 5.78 dB). The mean LogMAR value using the ETDRS chart was 0.43, whereas it was 0.38 using the PAM (P-value: 0.009).

Conclusions

VA values measured by the PAM were statistically significantly better than those measured by the ETDRS chart in eyes with ME secondary to various retinal vascular and uveitic diseases. VA measured by the PAM may be a more sensitive predictor of macular function than that obtained by ETDRS testing in eyes with ME.     

Effect of OCT volume scan density on thickness measurements in diabetic macular edema

Purpose

To evaluate the impact of reducing B-scan frame-sampling density on retinal thickness measurements using spectral domain optical coherence tomography (SD-OCT) in eyes with diabetic macular edema (DME).

Methods

We retrospectively collected OCT data for 64 eyes of 43 patients undergoing imaging for DME using the Cirrus HD-OCT 512 × 128 macular cube protocol. For each case, raw OCT data were imported into the 3D-OCTOR software, and retinal thickness maps were generated using all 128 B-scans and for lower densities of B-scans ranging from every other scan to only four scans (every 30-s B-scan). Maps were generated before and after manual correction of retinal boundary segmentation errors. The foveal central subfield (FCS) and total macular volume (TMV) values were used to compare thickness maps of varying densities.

Results

The mean difference in FCS retinal thickness and TMV increased as the B-scan density was reduced, particularly when the density was reduced to fewer than 16 B-scans over 6 mm. At a density of 16 B-scans, the mean absolute difference in FCS thickness was 2.43 μm (0.79%), with a maximum of 10.1 μm (4.09%). At this density, the mean difference in TMV was 0.012 mm³ (0.13%), with a maximum difference of 0.04 mm³ (0.47%). Manual correction of OCT segmentation errors resulted in a difference in FCS thickness of ≥10 μm in only 12.5% of cases, with a maximum difference of 115.7 μm.

Conclusion

A minimum of 16 equally spaced B-scans appear necessary to generate retinal thickness measurements similar to those produced using all 128 B-scans in eyes with DME. Manual correction of segmentation errors appeared to have a clinically meaningful effect in a small minority of cases. These results may have implications for the design of SD-OCT imaging and grading protocols in clinical trials of DME, particularly when using multiple SD-OCT instruments that acquire varying numbers of B-scans.     

Macular findings on optical coherence tomography in cat-scratch disease neuroretinitis

Purpose

To describe the macular findings on optical coherence tomography (OCT) in patients with cat-scratch disease (CSD) neuroretinitis.

Methods

Medical records of all patients diagnosed with CSD neuroretinitis at the Tel Aviv Medical Center between April 2006 and May 2010 were retrospectively reviewed. All patients underwent Stratus OCT macular examination.

Results

Eight eyes of seven patients with confirmed CSD neuroretinitis, (mean age 33±9.9 years, range 6–48 years) were included in the study. All patients presented clinically with optic nerve swelling and macular edema or macular exudates. OCT demonstrated flattening of the foveal contour, thickening of the neurosensory retina, and accumulation of subretinal fluid (SRF) in all studied eyes. Retinal exudates appeared as multiple hyper-reflective foci in the outer plexiform layer. The average central macular thickness was 460 μm (range 170–906 μm) and the average maximal retinal thickness was 613 μm (range 387–1103 μm), at presentation. The macula appeared normal on repeated exams during follow-up.

Conclusion

Similar OCT findings were demonstrated in patients with CSD neuroretinitis. SRF was found in all eyes, although was not visible on clinical examination or fluorescein angiography. OCT may be used as an adjunct imaging tool in the diagnosis and follow-up of patients with CSD neuroretinitis.     

Comparison of retinal nerve fiber layer measured by time domain and spectral domain optical coherence tomography in optic neuritis

Purpose

To study the relationship between retinal nerve fiber layer (RNFL) thickness measurements from time domain (Stratus) and spectral domain (Cirrus HD) optical coherence tomography (OCT) in subjects with optic neuritis.

Methods

A total of 18 patients who had suffered monocular acute optic neuritis were imaged by a single trained operator using the Stratus-OCT (fast RNFL scan mode) and Cirrus HD-OCT (optic disc cube mode) on the same day. The relationship between RNFL thickness measurements of the two OCTs (overall and by quadrants) were evaluated using intraclass correlation coefficient (ICC) and Bland–Altman plots. Comparisons between eyes having optic neuritis (ON-group) and fellow eyes (fellow-group) were assessed by a generalized estimating equation (GEE) regression model.

Results

For Stratus-OCT, the median average RNFL was 86.3 and 102 μ in the ON-group and in the fellow-group, respectively. For Cirrus-OCT, the corresponding measurements were 81 and 93 μ. Average RNFL thickness as determined by the two OCT devices was well correlated in the ON-group (ρ=0.906, P<0.001) and in the fellow-group (ρ=0.702, P=0.001). The median signal strength was significantly higher with Cirrus-OCT. Bland–Altman plots showed that Stratus RNFL measurements were larger than Cirrus-OCT, but smaller when average RNFL thickness was very thin (≤56 μ).

Conclusions

Although the Cirrus-OCT and Stratus-OCT RNFL thickness measurements are well correlated in patients with optic neuritis, RNFL measurements cannot be directly compared. Clinicians should be aware that measurements are generally higher with Stratus- than with Cirrus-OCT.     

Observational study of subclinical diabetic macular edema

Purpose

To determine the rate of progression of eyes with subclinical diabetic macular edema (DME) to clinically apparent DME or DME necessitating treatment during a 2-year period.

Methods

In all, 43 eyes from 39 study participants with subclinical DME, defined as absence of foveal center edema as determined with slit lamp biomicroscopy but a center point thickness (CPT) between 225 and 299 μm on time domain (Stratus, Carl Zeiss Meditec) optical coherence tomography (OCT) scan, were enrolled from 891 eyes of 582 subjects screened. Eyes were evaluated annually for up to 2 years for the primary outcome, which was an increase in OCT CPT of at least 50 μm from baseline and a CPT of at least 300 μm, or treatment for DME (performed at the discretion of the investigator).

Results

The cumulative probability of meeting an increase in OCT CPT of at least 50 μm from baseline and a CPT of at least 300 μm, or treatment for DME was 27% (95% confidence interval (CI): 14%, 38%) by 1 year and 38% (95% CI: 23%, 50%) by 2 years.

Conclusions

Although subclinical DME may be uncommon, this study suggests that between approximately one-quarter and one-half of eyes with subclinical DME will progress to more definite thickening or be judged to need treatment for DME within 2 years after its identification.     

Two-wavelength fundus autofluorescence and macular pigment optical density imaging in diabetic macular oedema

Purpose

To evaluate the application of 488 and 514 nm fundus autofluorescence (FAF) and macular pigment optical density (MPOD) imaging in diabetic macular oedema (DMO) and to demonstrate the typical imaging features.

Patients and Methods

A hundred and twenty-five eyes of 71 consecutive patients with diabetic retinopathy who underwent examination at a specialist university clinic employing a modified Heidelberg Retina Angiograph, using two different light sources of 488 and 514 nm wavelength, were retrospectively reviewed. MPOD images were calculated using modified Heidelberg Eye Explorer software. All images were evaluated by two independent masked graders. Features from FAF and MPOD images were correlated with optical coherence tomography (OCT) imaging findings and inter-grader variability, sensitivity and specificity were calculated using OCT as reference.

Results

Sixty-seven eyes had DMO on OCT. The inter-grader variability was 0.84 for 488 nm FAF, 0.63 for 514 nm FAF and 0.79 for MPOD imaging. Sensitivity and specificity for detection of DMO were 80.6 and 89.7% for 488 nm FAF; 55.2 and 94.8% for 514 nm FAF; and 80.6 and 91.4% for MPOD imaging. In 488 nm FAF and MPOD imaging, DMO was better visualised in comparison with 514 nm FAF imaging, P<0.01. MPOD revealed displacement of macular pigment by intraretinal cysts.

Conclusion

MPOD imaging, and particularly its combination with 488 nm and 514 nm FAF, provides a valuable addition to OCT in the evaluation of DMO and is clinically useful in rapid en-face assessment of the central macula.     

Clinical relevance of quantified fundus autofluorescence in diabetic macular oedema

Purpose

To quantify the signal intensity of fundus autofluorescence (FAF) and evaluate its association with visual function and optical coherence tomography (OCT) findings in diabetic macular oedema (DMO).

Methods

We reviewed 103 eyes of 78 patients with DMO and 30 eyes of 22 patients without DMO. FAF images were acquired using Heidelberg Retina Angiograph 2, and the signal levels of FAF in the individual subfields of the Early Treatment Diabetic Retinopathy Study grid were measured. We evaluated the association between quantified FAF and the logMAR VA and OCT findings.

Results

One hundred and three eyes with DMO had lower FAF signal intensity levels in the parafoveal subfields compared with 30 eyes without DMO. The autofluorescence intensity in the parafoveal subfields was associated negatively with logMAR VA and the retinal thickness in the corresponding subfields. The autofluorescence levels in the parafoveal subfield, except the nasal subfield, were lower in eyes with autofluorescent cystoid spaces in the corresponding subfield than in those without autofluorescent cystoid spaces. The autofluorescence level in the central subfield was related to foveal cystoid spaces but not logMAR VA or retinal thickness in the corresponding area.

Conclusions

Quantified FAF in the parafovea has diagnostic significance and is clinically relevant in DMO.     

Association of retinal vessel calibre and visual outcome in eyes with diabetic macular oedema treated with ranibizumab

Purpose

The study aims to identify the association between the baseline retinal vascular calibre and visual outcome of patients with diabetic macular oedema (DMO) treated with intravitreal ranibizumab.

Methods

The 1-M field (as defined in the ETDRS study) of the digital colour fundus photographs of DMO patients who had been treated primarily with ranibizumab in a clinical trial was assessed. Of the 84 patients, 25 had gradable retinal photographs that could be subjected to analyses by the Interactive Vessel Analysis (IVAN) software at baseline. The average retinal vascular calibre of the six largest venules (CRVE) and the six largest arterioles (CRAE) in the peripapillary area (0.5 and 1 disc diameter from the optic disc margin) was measured. The relationship between CRVE and CRAE at baseline and the change in visual acuity at month 12 was assessed using the Mann–Whitney U test.

Results

Ten eyes from 10 patients who had shown an improvement of ≥2 lines of best corrected visual acuity (BCVA) at month 12 had a wider baseline CRVE (248.3±24.5 μm) compared with the 15 eyes from 15 patients who did not show the improvement of ≥2 lines (226.6±44.8 μm, P<0.05). The baseline CRAE did not differ significantly in these patients (156.1±22.7 vs 142±17.5 μm, P=0.17).

Conclusions

A wider baseline retinal venular calibre may be a predictor of better visual outcome in DMO eyes treated with ranibizumab. Further prospective studies with a larger sample size and a broader range of disease severity and visual acuity are needed to confirm this finding.     

Fourier-domain optical coherence tomography of eyes with idiopathic epiretinal membrane: correlation between macular morphology and visual function

Purpose

The purpose of this study is to evaluate the macular morphological changes associated with idiopathic epiretinal membrane (iERM) using high-resolution Fourier-domain optical coherence tomography (FD-OCT), as they correlate with visual acuity and microperimetry (MP-1).

Methods

In all, 24 eyes (19 subjects) with iERM were imaged prospectively using FD-OCT with axial resolution of 4.5 μm and transverse resolution of 10 to 15 μm. MP-1 and Stratus OCT were carried out in a subset of eyes.

Results

The mean log of the minimum angle of resolution best-corrected visual acuity (BCVA) was 0.18±0.16 (range: −0.08 to 0.48, Snellen equivalent 20/15⁻¹ to 20/60). ERM was visualized in all 24 eyes with FD-OCT and in 17 eyes (85%) of 20 eyes imaged with Stratus OCT. Although BCVA correlated with macular thickening in the central 1 mm sub-field of the Stratus ETDRS (P=0.0005) and macular volume (central 3 mm area) on FD-OCT (P<0.0001), macular thickening on thickness map and volume correlated poorly with decrease in macular sensitivity on MP-1 (P=0.16). On FD-OCT, foveal morphological changes correlated best with decrease in BCVA, the strongest being central foveal thickness (P<0.0001). Other significant changes included blurring of the foveal inner segment–outer segment (IS–OS) junction and/or Verhoeff''s membrane, vitreal displacement of foveal outer nuclear layer and foveal detachment (P<0.05). Foveal IS–OS junction disruption was seen in 25% of eyes on Stratus OCT but in none of the eyes on FD-OCT.

Conclusion

FD-OCT allowed improved visualization of ERM and associated foveal morphological changes that correlated best with BCVA. Macular thickening correlated weakly with decreased macular function as assessed by MP-1.     

A new, pachymetry-based approach for diagnostic cutoffs for normal, suspect and keratoconic cornea

Purpose

To analyze whether an association exists between keratometric and pachymetric changes in the cornea, and whether it can be used to create pachymetric cutoff criteria secondary to keratometric criteria.

Methods

In this cross-sectional study, 1000 candidates presenting to the refractive surgery services of a tertiary care hospital underwent bilateral Orbscan IIz (Bausch and Lomb) assessment along with other ophthalmic evaluation.

Results

Stepwise regression analysis-based models showed that simulated keratometry (simK) astigmatism was significantly predicted by the minimum corneal thickness (MCT) and difference between central and MCT (δCT), mean SimK by the MCT and δCT, and maximum keratometry in the central 10-mm zone by the MCT and δCT (P<0.001). The mean MCT values were 542.5±39.6, 539.9±39.2, 524.2±49.5, and 449.3±73.7 μm for flatter normal (<44 D), steeper normal (≥44 D), keratoconus suspect and keratoconic eyes, respectively (P<0.001). The mean differences between central corneal thickness and MCT (δCT) were 12.2±7.1 μm, 12.4±7.4 μm, 14.4±8.9 μm and 23.2±10.1 μm for the flatter normal, steeper normal, keratoconus suspect, and keratoconic eyes, respectively (P<0.001). Mean and 2SD cutoff were used to suggest that a cornea having MCT<461 μm or δCT>27 μm has only a 2.5% chance of being normal and not a keratoconus suspect or worse.

Conclusion

Pachymetric diagnostic cutoffs can be used as adjuncts to the existing topographic criteria to screen keratoconus suspect and keratoconic eyes.     

Internal spherical aberration by ray tracing-type aberrometry in multifocal pseudophakic eyes

Purpose

To demonstrate the results of the ray tracing-type aberrometer in measuring spherical aberration (SA) in pseudophakic eyes with monofocal intraocular lens (IOL), aspheric monofocal IOL, or aspheric diffractive multifocal IOL.

Methods

Total, corneal, and internal SA were measured using iTrace at a 6-mm pupil size in 27 eyes of 27 patients implanted with a monofocal spherical IOL (group 1: Natural, SN60AT), 30 eyes of 30 patients implanted with a monofocal aspheric IOL (group 2: IQ, SN60WF), and 30 eyes of 30 patients implanted with a multifocal aspheric IOL (group 3: ReSTOR, SN6AD1) at 3 months after cataract surgery. We compared the internal SAs of these IOLs in pupil sizes of 3, 4, 5, and 6 mm.

Results

There were no demographic statistically significant differences among the groups. The internal SA of group 1 had a positive value. The internal SA of group 2 was −0.175±0.135 μm in 5-mm pupils and −0.227±0.253 μm in 6-mm pupils. The internal SA of group 3 was −0.072±0.128 μm in 5-mm pupils and −0.173±0.231 μm in 6-mm pupils.

Conclusion

Measuring internal SA with iTrace yields relatively accurate results in all types of IOLs with adequate pupil sizes.     

Optimizing evaluation of Lissamine Green parameters for ocular surface staining

Purpose

The recently published seminal dry eye workshop proceedings defined Lissamine Green (LG), an organic dye, as a gold standard for demonstrating ocular surface staining. The purpose of the current study was to determine the optimal parameters of 1% LG instillation for the ocular surface examination in dry eye patients.

Design

Prospective and observational quality improvement study.

Methods

A quality improvement study evaluated 16 eyes from eight dry eye patients with different levels of severity. LG (1%), in three volumes (5, 10, and 20 μl) was instilled into the conjunctival cul-de-sac, and four masked observers with different levels of clinical expertise examined the patients with and without red filter. The staining pattern of the conjunctiva and cornea was documented with the Oxford scale within 4 min of LG instillation. Optimal volume and inter-observer reliability were assessed.

Results

All dye volumes were tolerated well by all patients. Experienced observers preferred 10 μl volume because of the ease of examination and accuracy. Although instillation of 20 μl yielded similar scores as 10 μl, it resulted in overflow of the lid and facial skin staining. The use of red filter significantly improved reading scores (P<0.01). Inter-observer reliability was higher for conjunctival scores than for corneal scores for all patients. The highest reliability was demonstrated with 10 μl volume and increased with greater experience of the observer.

Conclusions

Ocular surface examination with instillation of 10 μl 1% LG has good inter-observer reliability and is well tolerated. Observation through a red filter facilitates the examination.     

Microperimetric changes in neovascular age-related macular degeneration treated with ranibizumab

Purpose

To assess the value of microperimetry in eyes with neovascular age-related macular degeneration previously treated with ranibizumab and now in the maintenance phase of therapy.

Methods

A total of 21 eyes (14 patients) were included. Microperimetry was performed using the Macular Integrity Assessment Device on at least three occasions for each eye. Intravitreal ranibizumab was administered if visual acuity (VA) or optical coherence tomography (OCT) showed signs of active disease.

Results

Five eyes showed no change in VA or OCT findings, and required no intravitreal injections. In these eyes, mean threshold sensitivity (TS) decreased by 13% (paired t-test, P=0.05) during the study period, but fixation stability (FS) was unchanged. In all, 16 eyes showed signs of disease activity, and therefore required ranibizumab injections during the study. In these eyes, VA, central retinal thickness (CRT), FS, and TS remained unchanged during follow-up. Peak TS was noted when CRT was 210 μm; above or below 210 μm, there was a gradual reduction in TS.

Conclusion

This study has provided novel information on the relationship between macular sensitivity, CRT, and VA in the maintenance phase of ranibizumab therapy. Patients with stable VA and CRT may still have deteriorating retinal sensitivity. This is usually a late manifestation and may indicate subclinical CNV activity.     

Phase 1 dose-escalation study of a siRNA targeting the RTP801 gene in age-related macular degeneration patients

Background

To evaluate the safety, tolerability, pharmacokinetics, and dose-limiting toxicities of a single intravitreal (IVT) injection of PF-04523655, a 19-nucleotide, O-methyl stabilized, double-stranded small interfering ribonucleic acid targeting the RTP801 gene in patients with neovascular age-related macular degeneration (AMD).

Methods

Prospective, phase 1, clinical multicentre trial, enrolled 27 patients with neovascular AMD unresponsive to prior treatment and best corrected visual acuity (BCVA) ≤20/200 in the study eye in stratum 1: (dose-escalating, open-label: 50 to 3000 μg of PF-04523655) and 27 patients who had potential to benefit from therapy and BCVA of ≤20/100 and ≥20/800 in stratum 2 (parallel, masked study of 1000, 1500, 2250, and 3000 μg of PF-04523655). The primary outcome was safety and tolerability assessment as well as pharmacokinetic profiling following a single IVT injection of PF-04523655.

Results

Doses of PF-04523655 ≥400 μg were generally detectable in the plasma at 1, 4, and 24 h post-injection. And all doses were below the lowest level of quantification by day 14. A single IVT injection of 50 to 3000 μg of PF-045237655 was generally safe and well tolerated over 24 months. There were no dose-limiting toxicities.

Conclusion

A single IVT injection of PF-0523655 ≤3000 μg seems safe and well tolerated in eyes with neovascular AMD.