Medical hypothesis discovery and innovation in ophthalmology

MicroPulse transscleral cyclophotocoagulation (IRIDEX Corp., Mountain View, CA) is a novel technique that uses repetitive micropulses of active diode laser (On cycles) interspersed with resting intervals (Off cycles). It has been proposed that the OFF cycles allow thermal dissipation and, therefore, reduce collateral damage. The literature suggests that Micropulse has a better safety profile compared to traditional continuous-wave cyclophotocoagulation. However, because it is a relatively new technique, there are no clear guidelines stating the ideal laser parameters that would allow the best balance between high and sustained effectiveness with minimal side effects. This research reviewed the literature to approximate ideal parameters for single-session treatment. To simplify the comparison between studies, this study used Joules (J) as a way to standardize the energy levels employed. The reviewed clinical publications allowed reduction of these parameters to a range between 112 and 150 J of total energy, which allows a moderate IOP lowering effect of around 30% with few/no complications. An additional narrowing of the parameters was achieved after analyzing recently published experimental data. These data suggest a different mechanism of action for the Micropulse, similar to that of the pilocarpine. This effect was maximum at 150 J. Since clinical studies show few or no complications, even at those energy levels, it could be hypothesized that the ideal parameters can be located at a point closer to 150 J. This data also leads to the concept of dosimetry; the capacity to dose mTSCPC treatment based on desired IOP lowering effect and risk exposure. Further prospective studies are needed to test the proposed evidence-based hypothesis.

The use of Rho Kinase (ROCK) inhibitors as therapeutic agents in ophthalmology has been a topic of discussion for several years, particularly in the realm of glaucoma, Fuchs’ endothelial dystrophy, and diabetic retinopathy. In this review, the authors provide a detailed and comprehensive overview of the published literature on the use of Rho kinase inhibitors for the aforementioned purposes. A thorough search of several databases was conducted to find sufficient literature on ROCK inhibitors. This research found strong evidence demonstrating that inhibition of Rho kinase significantly decreases IOP, increases healing of the corneal endothelium, and decreases progression of diabetic retinopathy. The main side effect of ROCK inhibitors is conjunctival hyperemia that is often present in more than half of the patients in certain formulations. Additional clinical trials investigating the reviewed treatment options of Rho kinase inhibitors are necessary to further validate previous findings on the topic. Nonetheless, it is clear that Rho kinase inhibitors have the potential to be another potent therapeutic option for several chronic diseases in ophthalmology.

This study investigated in-vivo changes of peripheral refraction with commercially available single vision and multifocal soft contact lenses, utilizing different designs and various corrective power values. Starting at the fovea, wave-front aberrations were measured up to 30o nasal retinal eccentricity, in 10o increments, using a commercially available Shack-Hartmann aberrometer. Three different types of contact lenses were fitted in an adult subject’s right eye: Acuvue Oasys Single Vision (ASV), Proclear Multifocal D with 2.50 diopters (D) add power (PMD), and ArtMost SoftOK (SOK). Each lens type was fitted in corrective power values of -2.00 D, -4.00 D, and -6.00 D. Refractive errors were computed in power vector notation: The spherical equivalent (M), the Cartesian Jackson-Cross-Cylinder (J0), and the oblique Jackson Cross Cylinder (J45) from measured second order Zernike terms. Acuvue Oasys Single Vision lenses produced a slight myopic shift at 30o retinal periphery (-0.32 D ± 0.05) without significant differences between the various lens power values. Proclear Multifocal D lenses did not create clinically significant myopic shifts of at least -0.25 D. All SOK lenses produced clinically significant relative myopic shifts at both 20o (-0.61 D ± 0.08) and 30o (-1.42 D ± 0.15) without significant differences between the various lens power values. For all lens types and power values, off-axis astigmatism J0 was increased peripherally and reached clinical significance beyond 20o retinal eccentricity. The increased amount of off-axis astigmatism J0 did not show a significant difference for the same type of lenses with different dioptric power. However, at 30o retinal eccentricity, SOK lenses produced significantly higher amounts of off-axis astigmatism J0, compared with ASV and PMD lenses (SOK versus ASV versus PMD: -1.67 D ± 0.09, -0.81 D ± 0.07, and -0.72 D ± 0.15). Both ASV and SOK lenses showed no clinically significant differences in the amount of introduced astigmatic retinal image blur, with various lens power values. Proclear Multifocal D lenses showed a systematic increase of astigmatic retinal image blur with an increase of add power. At 30o retinal eccentricity, -6.00 D SOK lenses introduced 0.73 D astigmatic retinal image blur, while PMD and ASV lenses introduced 0.54 D and 0.37 D, respectively. In conclusion, relative peripheral refractions, measured in-vivo, were independent of the contact lenses central corrective power. The SOK contact lenses demonstrated a stronger capability in rendering relative peripheral myopic defocus into far periphery, compared to the other lens designs used in this study. This was accompanied by higher amounts of introduced astigmatic retinal image blur.

Graft Versus Host Disease (GVHD) is an inflammatory immune disease, mediated by the donor’s immune cells and can arise after allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for the treatment of hematologic malignancies. It can lead to destructive manifestations in various tissues, particularly dermatological, gastrointestinal, and ocular tissues. The most common ocular morbidity is dry eyes, which is often the first manifestation of GVHD. Regulatory T cells (Tr) can be broadly classified as natural or adaptive (induced). After Bone-Marrow Transplantation (BMT), excessively increased levels of type 1 Tr (Tr1) are generally observed with absence of a GVHD, while low levels are seen with severe GVHD. Treatment of patients, undergoing BMT with Interleukin-10 (IL-10)-anergized donor T cells, led to immune reconstitution without the development of GVHD, which resulted in protection against infection and against the return of the cancer. Surprisingly, in both naive syngeneic mouse models of skin and cardiac allografts, graft retention was augmented after infusion of in vitro generated double-negative Tr (DN Tr). In addition, GVHD was reduced in mice with a genetic deficiency in the IL-27 receptor (IL-27R-/-) and in mice treated with anti-IL-27p28–specific antibody. Considering above mentioned findings we would suggest carrying out experiments, using animal models of GVHD, in order to evaluate the potential role of Tr, as an innovative approach to overcome severe ocular morbidity caused by ocular GVHD.

Sildenafil is one of the most commonly used drugs for sexual dysfunction or to increase libido, and it regulates endothelial nitric oxide synthase enzyme via selective phosphodiesterase-V inhibition. Sildenafil can be easily obtained without a medical indication or prescription yet it is not considered as a completely safe medication. Hemoptysis and hemorrhagic stroke are some important adverse effects of sildenafil. The case of the current report was a 67-year-old diabetic patient with simultaneous anterior and posterior segment hemorrhage after the use of 100 mg sildenafil citrate. Anterior chamber clearance and pars plana vitrectomy were performed for the patient because the hyphema and vitreous hemorrhage did not resolve during the follow-up period. There are very limited data available in the literature suggesting an increase in the risk of hyphema or vitreous hemorrhage due to the use of sildenafil. This is the first report that reveals the bleeding effect of sildenafil use in a patient with type 2 diabetes.

This study was designed to evaluate the efficacy of low-dose of oral acetylsalicylic acid (aspirin) with focal argon laser for the treatment of acute central serous chorioretinopathy (CSCR). In this prospective case-control study, 40 Patients with acute CSCR were classified randomly to two groups; group A with no treatment as the control group and group B with argon Laser in focal treatment once, followed by aspirin, 100 mg per day orally, with follow up period of 12 months by evaluation of visual acuity, and by Optical Coherence Tomography (OCT)  every three months for one year. Patients in second group treated with argon Laser and aspirin showed more clinically significant improvement in both visual acuity and OCT macular thickness by the end of follow up period when compared with the observational group. It was concluded that argon Laser with low-dose oral aspirin results in improvement of visual acuity and OCT macular thickness.

The aim of this study was to use Spectral Domain-Optical Coherence Tomography (SD-OCT) to measure the thickness of the Macular Inner Retinal Layer (MIRL) and compare the results between diabetic patients with no signs of retinopathy and healthy subjects. Overall, 47 type 2 diabetic patients without clinical signs of retinopathy were prospectively analyzed along with 36 healthy subjects. This study excluded patients with other systemic or ocular diseases. All patients had their MIRL thickness measured by RTVue-100 SD-OCT (7x7 mm macular grid). The MIRL thickness is provided by the ganglion cell complex scan (comprised of the retinal nerve fiber, ganglion cell, and inner plexiform layers). Only one eye was randomly selected if both were eligible for analysis. Mean age was similar between the two groups (diabetic patients: 57.3 ± 10.6 and control subjects: 60.2 ± 12.2 years) (P = 0.19). No significant differences regarding optic disc area and cup-to-disc ratio was observed in the comparison of the two groups (P ≥ 0.38 for both comparisons). In patients with diabetes, the average MIRL was significantly thinner when compared to controls (91.6 versus 96.2 micrometer (µm); P = 0.02). Regional analysis revealed superior and inferior MIRL to be significantly thinner in patients with diabetes than the controls (P ≤ 0.04). The juxtafoveal area was compromised (thinned) in 70% of diabetic eyes, classified as abnormal (P < 1%; compared to the device’s normative database). In conclusion, patients with type 2 diabetes without clinical evidence of retinopathy had lower MIRL average values when compared to the control group. This can be explained by the ischemia and retinal tissue injury caused by diabetes even in early stages of diabetic retinopathy, which can affect MIRL thickness. Possible implications of these findings on diagnosis and treatment of diabetic retinopathy requires further investigation.