Journal of Ophthalmic and Vision Research
Volume:15 Issue: 3, Jul-Sep 2020

To describe and analyze the microstructural changes in herpetic stromal keratitis (HSK) observed in vivo by spectral-domain ocular coherence tomography (SD-OCT) at different stages of the disease.

A prospective, cross-sectional, observational, and comparative SD-OCT analysis of corneas with active and inactive keratitis was performed, and the pathologic differences between the necrotizing and non-necrotizing forms of the disease were analyzed.

Fifty-three corneas belonging to 43 (81.1%) women and 10 (18.8%) men with a mean age of 41.0 years were included for analysis. Twenty-four (45.3%) eyes had active keratitis, and 29 (54.7%) had inactive keratitis; the majority (83.0%) had the non-necrotizing form. Most corneas (79.1%) with active keratitis showed stromal edema and inflammatory infiltrates. Almost half of the active lesions affected the visual axis, were found at mid-stromal depth, and had a medium density. By contrast, corneas with inactive keratitis were characterized by stromal scarring (89.6%), epithelial remodeling (72.4%), and stromal thinning (68.9%). In contrast to non-necrotizing corneas, those with necrotizing HSK showed severe stromal scarring, inflammatory infiltration, and thinning. Additionally, most necrotizing lesions (77.7%) affected the visual axis and had a higher density (P = 0.01).

Active HSK is characterized by significant epithelial and stromal thickening and the inactive disease manifests epithelial remodeling at sites of stromal thinning due to scarring. Necrotizing keratitis is characterized by distorted corneal architecture, substantial stromal inflammatory infiltration, and thinning. In vivo SD-OCT analysis permitted a better understanding of the inflammatory and repair mechanisms occurring in this blinding corneal disease.

Ozone is a trioxygen molecule that spontaneously degrades into oxygen and oxygen free radicals. This study was designed to assess the effects of topical ozone application on outcomes after corneal collagen cross-linking (CXL).

Enucleated fresh cadaver yearling sheep eyes (n = 28) were divided into five groups: control (C, n = 6), sham (S, n = 6), ozone only (Z, n = 6), CXL only (X, n = 5), and Ozone + CXL (ZX, n = 5). In all groups, except C, the epithelial layer was removed. In group Z, 20 μg/mL liquid ozone was topically applied. In group X, CXL was performed in the accelerated pulse mode. In group ZX, both CXL and ozone were applied. Post-interventional oxygen levels were determined and corneal confocal microscopy and optical coherence tomography were performed. Corneas were evaluated using light and electron microscopy.

Pre-interventional central corneal thickness (CCT) was highest in the control group and considerably similar in the remaining groups (P = 0.006). Pre- and post-interventional CCT were significantly different in the ozonated groups (Z and ZX) (P = 0.028; P = 0.043). Demarcation line depths were similar in groups Z, X, and ZX (P = 0.343). Increased stromal tissue reflectivity was observed in groups Z, X, and ZX. Oxygen levels were higher in the ozonated groups (Z and ZX) (P = 0.006), and caspase activity was higher in the CXL groups (X and ZX) (P = 0.028) as compared to the other groups. Group ZX showed tighter, more regular, and parallel fibrils.

Ozone increases corneal stromal oxygenation which can probably augment the effect of CXL. Future studies should investigate the safety and feasibility of ozone application during CXL.

Keratoconus (KC) is a bilateral and noninflammatory disease, characterized by progressive thinning and anterior protrusion of the cornea and may result in severe visual impairment due to irregular astigmatism. Matrix metalloproteinases (MMP) are the main group of enzymes that degrade extracellular matrix proteins including collagens; Type IV collagen is found in the corneal stroma. MMP enzymatic activity is inhibited by tissue inhibitor of metalloproteinase-1 (TIMP-1). A decrease in TIMP-1 level is associated with the development of KC. In the present study, we investigated the impact of COL4A4 rs2228557 C/T and TIMP-1 rs4898 C/T (X-chromosome) variants on the odds of KC development in a sample of Iranian population.

This case–control study was conducted on 140 patients with KC and 150 healthy control subjects. We used modified methods of Nested-PCR and ARMS-PCR in combination (Nested- ARMS-PCR) and confirmed their validity with RFLP–PCR.

Significant differences were noticed between KC patients and healthy individuals regarding the genotype TY or T allele frequencies of rs4898 in the male subjects (OR = 0.43, 95%CI: 0.20–0.92, P = 0.03), whereas no significant differences were identified in the female subjects (OR = 1.07, 95%CI: 0.52–2.20, P = 0.85). The rs2228557, T allele was associated with KC (OR = 0.69, 95% CI: 0.50–0.97, P = 0.035).

In the rs2228557 variant, T allele acts as a protective factor from the disease and decreases the risk of KC compared with the C allele. Also, in our investigation about rs4898, we found that TY genotype or T allele decreased the risk of KC compared with the C allele in males and was a protective factor for KC in our population.

To evaluate the effect of asphericity and blue light filter (BLF) of three different intraocular lenses (IOLs) on the visual performance, second- and third-order aberrations (defocus, coma, trefoil), and contrast sensitivity after uneventful cataract surgery.

One hundred and twenty eyes of 60 patients with clinically significant cataract were randomly assigned to receive one of the three IOL types: Bioline Yellow Accurate (aspheric, with BLF, i-medical, Germany), BioAcryl 60125 (spherical, without BLF, Biotech, France), and H65C/N (aspheric, without BLF, PhysIOL, Belgium). Each IOL was implanted in 40 eyes. Complete ophthalmologic examination, functional acuity contrast testing and wavefront analysis were performed 60 days postoperatively.

The mean postoperative best-corrected visual acuity (BCVA) was 0.95 ± 0.08, not differing statistically among the IOL groups (P = 0.83). Mean defocus and coma values did not yield any statistically significant difference through the IOL groups varying from –0.784 to –0.614 μm and 0.129 to 0.198 μm (P = 0.79 and 0.34, respectively). Bioline Yellow Accurate IOL presented less trefoil aberrations, 0.108 ± 0.05 μm, compared to the other two IOL types (BioAcryl [0.206 ± 0.19 μm] and Physiol [0.193 ± 0.17 μm], P < 0.05). Contrast sensitivity values did not differ among the groups under all lighting conditions. Bioline Yellow IOL showed a statistically higher loss of contrast sensitivity (between mesopic and mesopic with glare conditions) compared to the BioAcryl and PhysIOL in 12 and 3 cpd spatial frequencies, respectively (P < 0.05).

Bioline Yellow IOL indicated lower contrast sensitivity under mesopic conditions when glare was applied but resulted in less trefoil aberrations after uneventful cataract surgery. No further differences were noted in postoperative visual performance among three IOL groups.

To assess intraocular pressure (IOP) changes after the water drinking test (WDT) in patients with primary congenital glaucoma (PCG).

In this prospective interventional study, 20 eyes of 20 patients with PCG were included. All patients had undergone trabeculotomy. Six out of twenty eyes had received a glaucoma drainage device (GDD) implantation. IOP was measured using an air-puff tonometer at baseline, and 15, 30, 45, and 60 min after WDT. The repeated-measures analysis of variance test was used to compare the mean IOPs at different time points.

The mean (± standard deviation) of participants’ age was 9.9 ± 2.7 years (range, 6 to 16 years), and 8 (40%) participants were male. The mean IOPs at baseline and 15, 30, 45, and 60 minutes after the WDT were 15.8 ± 3.7, 18.6 ± 3.4, 19.0 ± 3.8, 17.9 ± 3.8, and 16.9 ± 3.5 mmHg, respectively (P < 0.001). Pairwise comparisons revealed that the mean IOPs after 15 and 30 min were significantly greater than the baseline IOP (P < 0.001 and P = 0.002, respectively); however, the difference in mean IOPs after 45 and 60 min were not statistically significant from the baseline IOP. The averages of IOP peak and IOP fluctuation after the WDT were 20.0 ± 3.5 and 4.2 ± 2.9 mmHg, respectively. IOP fluctuation in those who underwent trabeculotomy alone was twice that of those with GDDs, but the difference was not statistically significant (5.0 vs 2.5 mmHg; P = 0.08).

In patients with PCG, WDT induced significant IOP elevation 15 and 30 min after the test, which returned to pre-test values after 45 min.

To evaluate the long-term visual outcomes of ab externo trabeculotomy for primary congenital glaucoma (PCG) at a single pediatric ophthalmology center.

In this retrospective single-center case series, data from 63 eyes of 40 patients who underwent ab externo trabeculotomy between September 2006 and June 2018 were included. The data were analyzed for best corrected visual acuity (BCVA), stereopsis, and surgical success. Kaplan–Meier analysis was performed using the surgical success criteria defined as intraocular pressure (IOP) ≤ 21 mmHg and ≥ 20% below baseline without the need for additional glaucoma surgery.

BCVA at the time of diagnosis was 0.37 ± 0.48 logMAR, which changed to 0.51 ± 0.56 logMAR at the final follow-up (P = 0.08). Twenty-five percent of patients had BCVA equal to or better than 20/40 at the final visit. The mean refraction at baseline was –4.78 ± 5.87 diopters, which changed to less myopic refraction of –2.90 ± 3.83 diopters at the final visit. Optical correction was prescribed in 66% of eyes at the final visit. The average final stereopsis was 395.33 sec of arc. The linear regression model showed a significant association between the surgery success rate and final BCVA as well as stereoacuity (Pvalues: 0.04 and 0.03, respectively). Intraocular pressure (IOP) decreased significantly from 29.79 ± 7.67 mmHg at baseline to 16.13 ± 3.41 mmHg at the final follow-up (P = 0.001).

Patients with PCG can achieve an acceptable visual acuity and stereoacuity, particularly in cases of timely intervention and close follow-up.

This study describes the long-term visual and anatomic outcomes of antivascular endothelial growth factor (VEGF) treatment using a treat and extend dosing regimen.

This cross-sectional cohort study consisted of 224 treatment-naïve eyes with neovascular age-related macular degeneration (NV-AMD) from 202 patients that were treated with anti-VEGF agents bevacizumab, ranibizumab, and aflibercept using a treat and extend (TAE) regimen by four physician investigators in a large urban referral center from 2008 to 2015. Subjects were evaluated for visual acuity, injection frequency, and optical coherence tomography (OCT).

Over a seven-year follow-up period (mean 3.4 years), an average 20.2 ± 14.7 injections were administered with 8.4 injections in the first year and 5.5 injections by the seventh year of remaining eyes undergoing treatment. Visual acuity was 0.70 logMAR (20/100 Snellen) at the first visit and 0.67 logMAR (20/93 Snellen) at the final visit, with 74% of eyes maintaining or gaining more than 2 lines of vision. Long-term, 45.1% of eyes achieved 20/50 or better, while 27.1% were 20/200 or worse. Of the treated patients, 61.2% received monotherapy with no difference in visual acuity outcomes or number of injections between the agents used. OCT analysis showed decreased fluid from initial to final follow-up visit: 70.1–15.6% with sub-retinal fluid (SRF) and 47.3–18.8% with intraretinal fluid (IRF) with no difference between the agents were used.

This study demonstrates that most patients (74%) improve or maintain visual acuity long-term using a TAE model with a significant portion (45.1%) achieving 20/50 or better visual acuity with sustained treatment.

To evaluate the safety of intravitreal injection of Stivant, a biosimilar to bevacizumab, in rabbits using electrophysiological and histological analysis.

Both eyes of 41 New Zealand albino rabbits were injected with 0.1 mL (2.5 mg) of Stivant. The rabbits were scheduled to be sacrificed 1, 2, 7, 14, and 28 days after injection for histopathological evaluations. Clinical examinations and electroretinography (ERG) were performed at baseline and just before sacrificing the rabbits. Fourteen separate rabbits received a reference drug (Avastin) and were considered as the control group. Furthermore, three other rabbits received the same volume of saline (saline control group). Rabbits of both control groups were sacrificed four weeks after injection. ERG was performed 1, 2, 7, 14, and 28 days after injections.

No significant difference was observed in a- and b-wave amplitudes and latency after intravitreal Stivant injection between baseline and different time points. Moreover, there was no statistically significant difference in wave amplitudes and latency between the Stivant and control groups. The histology of rabbit eyes of the Stivant and control groups after intravitreal injections was not distinguishable.

The biosimilar Stivant, up to a dose of 2.5 mg, did not appear to be toxic to the retina in albino rabbits. These results suggest that this drug could be a safe and inexpensive alternative to intravitreal bevacizumab. The efficacy of these injections was not investigated in this study and needs to be evaluated in future studies.

To compare the choroidal thickness among eyes with retinitis pigmentosa (RP), Stargardt disease, Usher syndrome, cone-rod dystrophy, and healthy eyes of sex- and age-matched individuals.

In this comparative study, 503 eyes with RP (n = 264), cone-rod dystrophy (n = 109), Stargardt disease (n = 76), and Usher syndrome (n = 54) were included. To validate the data, 109 healthy eyes of 56 sex- and age-matched individuals were studied as controls. Choroidal imaging was performed using enhanced depth imaging-optical coherence tomography. Choroidal thickness was measured manually using MATLAB software at 13 points in nasal and temporal directions from the foveal center with the interval of 500 µm and the choroidal area encompassing the measured points was calculated automatically.

The mean age was 36.33 ± 13.07 years (range, 5 to 72 years). The mean choroidal thickness at 13 points of the control eyes was statistically significantly higher than that in eyes with RP (P < 0.001) and Usher syndrome (P < 0.05), but not significantly different from that in eyes with Stargardt disease and cone-rod dystrophy. Among different inherited retinal dystrophies (IRDs), the choroidal thickness was the lowest in eyes with RP (P < 0.001). Choroidal thickness in the subfoveal area correlated negatively with best-corrected visual acuity (r = −0.264, P < 0.001) and the duration of ocular symptoms (r = −0.341, P < 0.001) in all studied IRDs. No significant correlation was observed between the subfoveal choroidal thickness and central macular thickness (r = −0.24, P = 0.576).

Choroidal thinning in four different types of IRDs does not follow a similar pattern and depends on the type of IRD and the duration of ocular symptoms. A larger cohort is required to verify these findings.

To evaluate the pattern-reversal visual evoked potential (PRVEP) in lowcontrast, spatial frequencies in time, frequency, and time-frequency domains.

PRVEP was performed in 31 normal eyes, according to the International Society of Electrophysiology of Vision (ISCEV) protocol. Test stimuli had checkerboard of 5% contrast with spatial frequencies of 1, 2, and 4 cycles per degree (cpd). For each VEP waveform, the time domain (TD) analysis, Fast Fourier Transform(FFT), and discrete wavelet transform (DWT) were performed using MATLAB software. The VEP component changes as a function of spatial frequency (SF) were compared among time, frequency, and time–frequency dimensions.

As a consequence of increased SF, a significant attenuation of the P100 amplitude and prolongation of P100 latency were seen, while there was no significant difference in frequency components. In the wavelet domain, an increase in SF at a contrast level of 5% enhanced DWT coefficients. However, this increase had no meaningful effect on the 7P descriptor.

At a low contrast level of 5%, SF-dependent changes in PRVEP parameters can be better identified with the TD and DWT approaches compared to the Fourier approach. However, specific visual processing may be seen with the wavelet transform.

Conjunctivitis is a commonly encountered condition in ophthalmology clinics throughout the world. In the management of suspected cases of conjunctivitis, alarming signs for more serious intraocular conditions, such as severe pain, decreased vision, and painful pupillary reaction, must be considered. Additionally, a thorough medical and ophthalmic history should be obtained and a thorough physical examination should be done in patients with atypical findings and chronic course. Concurrent physical exam findings with relevant history may reveal the presence of a systemic condition with involvement of the conjunctiva. Viral conjunctivitis remains to be the most common overall cause of conjunctivitis. Bacterial conjunctivitis is encountered less frequently and it is the second most common cause of infectious conjunctivitis. Allergic conjunctivitis is encountered in nearly half of the population and the findings include itching, mucoid discharge, chemosis, and eyelid edema. Long-term usage of eye drops with preservatives in a patient with conjunctival irritation and discharge points to the toxic conjunctivitis as the underlying etiology. Effective management of conjunctivitis includes timely diagnosis, appropriate differentiation of the various etiologies, and appropriate treatment.

In this “Perspective”, we discuss ocular gene therapy – the patient’s perspective, the various strategies of gene replacement and gene editing, the place of adenoassociated virus vectors, routes of delivery to the eye and the remaining question - “why does immunity continue to limit efficacy?” Through the coordinated efforts of patients, researchers, granting agencies and industry, and after many years of pre-clinical studies, biochemical, cellular, and animal models, we are seeing clinical trials emerge for many previously untreatable heritable ocular disorders. The pathway to therapies has been led by the successful treatment of the RPE65 form of Leber congenital amaurosis with LUXTURNATM. In some cases, immune reactions to the vectors continue to occur, limiting efficacy. The underlying mechanisms of inflammation require further study, and new vectors need to be designed that limit the triggers of immunity. Researchers studying ocular gene therapies and clinicians enrolling patients in clinical trials must recognize the current limitations of these therapies to properly manage expectations and avoid disappointment, but we believe that gene therapies are well on their way to successful, widespread utilization to treat heritable ocular disorders.

The COVID-19 pandemic necessitates implementation of exposure control measures in all facets of the healthcare sector. Healthcare professionals who work in busy ophthalmology clinics and theaters are amidst the highest at-risk of contracting COVID- 19. The authors review the up-to-date scientific evidence of SARS-CoV-2 transmission to demystify and explain the exposure control options available for ophthalmic workplace and offer insights from an industrial hygiene standpoint. As the we enter the post-COVID world, these measures will be critical to enhance workplace safety, and thus protect patients and staff alike.

To report a case of refractory ocular hypotony due to chronic Behcet’s disease with good response to high-dose topical latanoprost.

We present a 26-year-old man with a known history of Behcet’s disease who developed decreasing vision and severe ocular hypotony that was refractory to multiple treatment modalities including subtenon triamcinolone acetonide, ibopamine, pars plana vitrectomy, and silicone oil injection. We decided to try high-dose topical latanoprost for the management of ocular hypotony based on recent reports. After six months, intraocular pressure (IOP) increased by 5 mm Hg, became stable at 7 mm Hg, and remained unchanged at month 24.

High-dose topical latanoprost could lead to significant increase in IOP in uveitis-induced refractory ocular hypotony.

Orbital cellulitis (OC) is a rare postoperative complication of glaucoma drainage device (GDD) implantation. To date, there have only been 10 reported cases of OC following GDD implantation.

Here, we report a case of OC in a 57-year-old man who developed pain, proptosis, and limited extraocular motility two days after uneventful Ahmed FP7 implantation in the right eye. Contrast-enhanced computed tomography of the orbits demonstrated fat stranding and a small fluid collection, consistent with OC. He had minimal improvement with intravenous antibiotics and ultimately underwent GDD explantation. A systematic review of the literature showed that the development of OC following GDD implantation can occur in the early or late postoperative period. Immediate hospitalization with intravenous administration of broad-spectrum antibiotics is recommended. Explantation of the infected GDD is often required for source control.

OC is a rare postoperative complication of GDD implantation. Prompt evaluation and treatment are required, often combined with GDD explantation.

To report a case of choroidal osteoma associated with reactivation of choroidal neovascularization (CNV) and development of focal choroidal excavation (FCE).

A 34-year-old woman with choroidal osteoma complicated by CNV in the right eye for two years presented with deterioration of visual acuity in her right eye. A small retinal hemorrhage accompanied by subretinal fluid (SRF) was seen in the macular area of the right eye. Optical coherence tomography (OCT) showed that the inner retina was intact, and the outer retinal layers had outward displacement. SRF and a wedgeshaped choroidal depression were also seen. This choroidal excavation was not present on previous OCT images. The integrity of the inner retinal layers was maintained, and an optically clear space was present between the neurosensory retina and the retinal pigment epithelium.

Choroidal osteoma can be complicated by CNV and FCE could occur as a consequence. Again, FCE can lead to CNV development. This cascade can deteriorate vision and sometime lead to permanent visual loss.