Hyperopic Shift In Refractive Error Research Articles

Does Long-Duration Exposure to Microgravity Lead to Dysregulation of the Brain and Ocular Glymphatic Systems?

Spaceflight-associated neuro-ocular syndrome (SANS) has been well documented in astronauts both during and after long-duration spaceflight and is characterized by the development of optic disc edema, globe flattening, choroidal folds, and hyperopic refractive error shifts. The exact mechanisms underlying these ophthalmic abnormalities remain unclear. New findings regarding spaceflight-associated alterations in cerebrospinal fluid spaces, specifically perivascular spaces, may shed more light on the pathophysiology of SANS. The preliminary results of a recent brain magnetic resonance imaging study show that perivascular spaces enlarge under prolonged microgravity conditions, and that the amount of fluid in perivascular spaces is linked to SANS. The exact pathophysiological mechanisms underlying enlargement of perivascular spaces in space crews are currently unclear. Here, we speculate that the dilation of perivascular spaces observed in long-duration space travelers may result from impaired cerebral venous outflow and compromised cerebrospinal fluid resorption, leading to obstruction of glymphatic perivenous outflow and increased periarterial cerebrospinal fluid inflow, respectively. Further, we provide a possible explanation for how dilated perivascular spaces can be associated with SANS. Given that enlarged perivascular spaces in space crews may be a marker of altered venous hemodynamics and reduced cerebrospinal fluid outflow, at the level of the optic nerve and eye, these disturbances may contribute to SANS. If confirmed by further studies, brain glymphatic dysfunction in space crews could potentially be considered a risk factor for the development of neurodegenerative diseases, such as Alzheimer’s disease. Furthermore, long-duration exposure to microgravity might contribute to SANS through dysregulation of the ocular glymphatic system. If prolonged spaceflight exposure causes disruption of the glymphatic systems, this might affect the ability to conduct future exploration missions, for example, to Mars. The considerations outlined in the present paper further stress the crucial need to develop effective long-term countermeasures to mitigate SANS-related physiologic changes during long-duration spaceflight.

MicroRNA‐mRNA genetic networks in refractive eye development and myopia

AbstractPurposeMyopia is a complex disease controlled by both environmental and genetic factors. Recent genetic studies suggested that the development of myopia is controlled by numerous coding genes. However, the contribution of non‐coding genes, such as microRNAs, is poorly understood. The purpose of this study was to investigate the role of microRNAs in refractive eye development and the development of myopia.MethodsDifferential expression of both microRNAs and mRNAs was analyzed in the retina, RPE, choroid, and sclera of C57BL mice upon induction of experimental myopia with −20 D lenses using RNA‐seq and microRNA‐mRNA genetic networks were reconstructed. We also explored the impact of microRNAs on signaling pathways and evaluated the role of microRNAs in refractive eye development in vivo using conditional Dicer1 knockout mice.ResultsGene expression profiling revealed large number of differential mRNAs and microRNAs in the retina and RPE/choroid/sclera complexes. MicroRNAs were involved in the regulation of several key canonical pathways and biological processes previously implicated in refractive eye development. We then compared visual acuity, contrast sensitivity, and refractive errors in Dicer1 knockouts (Dicer1−/−) and wild‐type littermates (Dicer1+/+) at baseline. We found that loss of miRNAs in the postnatal eyes resulted in a large hyperopic shift in refractive error (+16.3 ± 3.6 D in Dicer1 knockouts versus +4.7 ± 3.0 D in wild‐type animals, p < 1.44 × 10−4), which was accompanied by a small reduction in visual acuity (0.360 ± 0.006 cpd in Dicer1−/− versus 0.403 ± 0.002 cpd in Dicer1+/+, p < 1.16 × 10−7) and contrast sensitivity (12.01 ± 0.27 in Dicer1−/− versus 13.65 ± 0.40 in Dicer1+/+, p < 1.91 × 10−5). Loss of miRNAs also caused a statistically significant increase in susceptibility to form‐deprivation myopia in Dicer1 knockouts compared to wild‐type animals (−19.1 ± 6.8 D in Dicer1−/− versus −9.7 ± 2.7 D in Dicer1+/+, p < 1.51 × 10−4).ConclusionsOur data suggest that microRNAs play significant role in refractive eye development and the development of myopia via modulation of several canonical signaling pathways. MicroRNAs appear to be integrated in the signaling cascade involved in the optical‐defocus‐regulated refractive eye development at multiple levels.

The odyssey of the ocular and cerebrospinal fluids during a mission to Mars: the "ocular glymphatic system" under pressure.

A significant proportion of the astronauts who spend extended periods in microgravity develop ophthalmic abnormalities including optic disc edema, globe flattening, chorioretinal folds, and hyperopic refractive error shifts. A constellation of these neuro-ophthalmic findings has been termed "spaceflight-associated neuro-ocular syndrome". Understanding this syndrome is currently a top priority for NASA, especially in view of future long-duration missions (e.g., Mars missions). The recent discovery of an "ocular glymphatic system" can potentially help to unlock mechanisms underlying microgravity-induced optic disc edema. Indeed, a major paradigm shift is currently occurring in our understanding of transport of fluids and solutes through the optic nerve following the recent discovery of an optic nerve glymphatic pathway for influx of cerebrospinal fluid. In addition, the recent identification of an entirely new glymphatic pathway for efflux of ocular fluid may have profound implications for fluid dynamics in the eye. Observations pertaining to this ocular glymphatic pathway provide critical new insights into how intracranial pressure can alter basic fluid transport in the eye. We believe that these novel findings have the potential to be game changers in our understanding of the pathogenesis of optic disc edema in astronauts. In the present review, we integrate these new insights with findings on the intracranial and neuro-ophthalmologic effects of microgravity in one coherent conceptual framework. Further studies in this area of investigation could not only provide exciting new insights into the mechanisms underlying microgravity-induced optic disc edema but also offer opportunities to develop countermeasure strategies.

Potential Involvement of the Ocular Glymphatic System in Optic Disc Edema in Astronauts.

INTRODUCTION: A significant proportion of the astronauts who spend extended periods in microgravity develop ophthalmic abnormalities, including optic disc edema, optic nerve sheath distention, globe flattening, chorioretinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts. A constellation of these neuro-ophthalmic findings has been termed spaceflight-associated neuro-ocular syndrome. An increased understanding of factors contributing to this syndrome is one of the top priorities for ESA and NASA because the length of missions is expected to increase substantially in the future. As discussed in the present article, the very recent discovery of an ocular glymphatic clearance system can potentially help to unlock mechanisms underlying microgravity-induced optic disc edema. Observations pertaining to the ocular glymphatic pathway provide supporting evidence for the hypothesis, originally proposed by our group, suggesting that the glymphatic outflow from the eye into the optic nerve may be impeded under prolonged microgravity conditions, leading to optic disc edema.Wostyn P, De Winne F, Stern C, Mader TH, Gibson CR, De Deyn PP. Potential involvement of the ocular glymphatic system in optic disc edema in astronauts. Aerosp Med Hum Perform. 2020; 91(12):975977.

Space flight-associated neuro-ocular syndrome (SANS)

Interesting novel and somewhat perplexing physiologic and pathologic neuro-ocular findings have been documented in astronauts during and after long duration space flight (LDSF). These findings collectively have been termed the "space flight-associated neuro-ocular syndrome" (SANS). The National Aeronautics and Space Administration (NASA) in the United States has meticulously and prospectively documented the clinical, ultrasound, optical coherence tomography imaging, and radiographic findings of SANS including unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts (i.e., cotton wool spots). NASA and collaborating researchers continue to study SANS in preparation for future manned missions to space, including continued trips to the ISS, a return to the moon, or perhaps new voyages to the asteroid belt, or the planet, Mars.

Choroidal folds. A presentation of two cases

Clinical caseWe report two patients of 29 and 50 years old presenting with unilateral choroidal folds in posterior segment in which, after a complete ophthalmic examination, we suspected an acquired hyperopic shift syndrome. Fluorescein angiography and magnetic resonance imaging revealed a flattening of posterior globes and distended perineural subarachnoid spaces. DiscussionAcquired hyperopia with choroidal folds is a benign condition characterised by the acute development of a unilateral or bilateral hyperopic shift in refractive error. We emphasise the importance of a differential diagnosis from a wide variety of disorders that can mimic this syndrome.

Pliegues coroideos. A propósito de dos casos

Clinical case We report two patients of 29 and 50 years old presenting with unilateral choroidal folds in posterior segment in which, after a complete ophthalmic examination, we suspected an acquired hyperopic shift syndrome. Fluorescein angiography and magnetic resonance imaging revealed a flattening of posterior globes and distended perineural subarachnoid spaces. Discussion Acquired hyperopia with choroidal folds is a benign condition characterised by the acute development of a unilateral or bilateral hyperopic shift in refractive error. We emphasise the importance of a differential diagnosis from a wide variety of disorders that can mimic this syndrome.

Emmetropization in chicks uses optical vergence and relative distance cues to decode defocus

When visual information is confined to one object plane, the emmetropization end-point is adjusted in accord with the corresponding incident optical vergence at the eye [Proceedings of the 7th International Conference on Myopia (2000) 113]. We now report the effect of adding extra visual information beyond the target plane. Visual conditions were controlled using a cone–lens system: black Maltese cross targets on white opaque backgrounds (OMX) were attached to the open faces of 2.5 cm translucent cones fitted with either 0, +25 or +40 D imaging lenses. An alternative target (TMX) was made by substituting the opaque target background for a transparent background, which allowed access to visual information beyond the target plane. The imaging devices were applied to 7-day-old chicks and worn for 4 days. Prior to this treatment, on day 2, some chicks underwent ciliary nerve section (CNS) to preclude accommodation. All treatments were monocular. Refractive errors and axial ocular dimensions were measured using retinoscopy and A-scan ultrasonography under halothane anesthesia. Treatment effects were specified as mean ( ±S.D.) interocular differences. Eyes with the OMX/+40 D lens combination remained emmetropic (+0.73 ±3.57 D), consistent with the target plane being approximately conjugate with the retina. Switching to the TMX caused a hyperopic shift in refractive error (+3.78 ±3.41 D). This relative shift towards hyperopia in switching from the OMX to the TMX target also occurred for the other two lens powers. Thus, the OMX/+25 D lens induced myopia (−7.00 ±5.88 D), corresponding to the imposed hyperopic defocus (target plane now imaged behind the retina), and switching to the TMX resulted in a reduction in myopia (−1.73 ±5.36 D). The OMX/0 D lens combination produced the largest myopic shift, and here, switching to the TMX condition almost eliminated the myopic response (−15.50 ±6.62 D cf. −0.56 ±1.24 D). This relative hyperopic shift associated with switching from the OMX to the TMX target was eliminated by CNS surgery. Thus, the two CNS/TMX groups were both more myopic than the equivalent no CNS/TMX groups (+40 D lens: −2.66 ±2.34 D; +25 D lens: −7.97 ±6.87 D). When the visual information is restricted to one plane, incident optical vergence appears to direct emmetropization. Adding visual information at other distances produces a shift in the end-point of emmetropization in the direction of the added information. That these effects are dependent on the integrity of the accommodation system implies that accommodation plays a role in emmetropization and represents the first reported evidence of this kind.

Refractive Changes during 72-hour Exposure to High Altitude after Refractive Surgery

The authors prospectively analyzed refractive and pachymetric parameters during exposure to high altitude after radial keratotomy (RK) and photorefractive keratectomy (PRK). The authors measured manifest and cycloplegic refraction, keratometry, computed video keratography, and central and peripheral pachymetry in six subjects who have undergone RK (11 eyes), six who have undergone PRK (12 eyes), and nine with myopia (17 eyes) at sea level and on three consecutive days at 14,100 feet. All measurements were repeated 1 week after subjects returned to sea level. Subjects who have undergone RK demonstrated a significant and progressive increase in spherical equivalence (+0.30 +/- 0.50 diopters on day 1 and +1.52 +/- 1.01 diopters on day 3; P < 0.001) and a decrease in keratometry values during exposure to altitude when compared with control subjects with myopia. Healthy subjects and those who have had PRK demonstrated no significant change in refractive error. Pachymetry measurements demonstrated significant peripheral corneal thickening in all three groups (RK, P < 0.004; PRK, P < 0.007; control subjects, P = 0.0006) by day 3 at high altitude. Refraction, keratometry, and pachymetry returned to baseline (P = 1.000) after return to sea level. Seventy-two-hour exposure to high altitude in subjects who have had RK induces a significant, progressive, and reversible hyperopic shift in refraction with corresponding video keratographic and keratometric changes. The authors hypothesize that the high-altitude hypoxic environment causes increased corneal hydration in the area of the RK incisions, which may lead to central corneal flattening and a hyperopic shift in refractive error. Subjects who have had PRK and those with myopia are not susceptible to this refractive shift. The authors' RK data suggest that the time since surgery and the amount of surgery are related to the degree of hyperopic shift during altitude exposure.

Ocular Symptoms and Signs Associated With Suramin Sodium Treatment for Metastatic Cancer of the Prostate

Therapy with suramin sodium has been associated with photophobia, iritis, optic atrophy, and vortex keratopathy. We studied the ocular findings in patients who underwent treatment with suramin sodium for metastatic cancer of the prostate. In a prospective study, 114 patients who underwent treatment with suramin sodium for cancer of the prostate had an ophthalmologic examination with two weeks of onset of treatment and two weeks after termination of therapy. Additional examinations were performed on patients who developed ocular symptoms during suramin sodium therapy. Nineteen (16.6%) of 114 patients developed ocular symptoms and signs while taking suramin sodium. Thirteen of these patients developed bilateral corneal epithelial whorllike deposits. In ten patients, the corneal deposits were associated with foreign body sensation and lacrimation. Symptoms in all of these patients resolved with topical lubricants. Three patients developed asymptomatic corneal deposits. Seven patients had blurred vision and were found to have a mean hyperopic shift in refractive error of 1.13 +/- 0.45 diopters (range, 0.75 to 2.00 diopters) that persisted throughout their treatment course. None of these patients had a decrease in best-corrected visual acuity. In this study, ocular symptoms and signs associated with suramin sodium were common but were not considered a dose-limiting toxicity. Hyperopic shift in refractive error is a previously unreported ocular finding in association with suramin sodium therapy.

Therapeutic Uses of the Excimer Laser Photorefractive Keratectomy

Phototherapeutic keratectomy (PTK) has been used to improve vision and reduce ocular symptoms in a variety of disorders. These include corneal dystrophies, scars, nodules, recurrent erosions, surgically induced astigmatism, and active infections. Using the criteria of two lines of improvement in best-corrected visual acuity, successful outcomes in large series range from approximately 60% to 80% of patients. PTK can obviate the need for penetrating or lamellar keratoplasty in over 70% of patients. Complications include a hyperopic shift in refractive error, corneal scarring, irregular astigmatism, corneal infection/ulceration, induced astigmatism, glare, and reactivation of herpes simplex. PTK has become a useful surgical tool for the treatment of corneal disorders. It can delay or eliminate the need for more invasive procedures, such as penetrating keratoplasty.

Refractive Changes at Extreme Altitude After Radial Keratotomy

We studied the effects of altitude on four corneas that had undergone radial keratotomy and four normal corneas exposed to increasing elevation during a high-altitude excursion. We measured visual acuity, cycloplegic refraction, keratometry, and intraocular pressure at sea level and after 24-hour exposure to 12,000 and 17,000 ft. We observed a significant increase in spherical equivalence (hyperopic shift) in radial keratotomy eyes exposed to altitude as compared to controls (P < .0001). The average change in spherical equivalent cycloplegic refraction from sea level to 12,000 ft was 1.03 +/- 0.16 diopters and from sea level to 17,000 ft was 1.94 +/- 0.26 diopters. We also observed a significant decrease in keratometry values at altitude as compared with control corneas (P < .0001). The average change in keratometry from sea level to 12,000 ft was 0.59 +/- 0.19 diopter and from sea level to 17,000 ft was 1.75 +/- 0.27 diopters. Although the specific origin of these changes is open to question, we hypothesize that hypoxic corneal expansion in the area of the radial keratotomy incisions may lead to central corneal flattening and a hyperopic shift in refractive error. The cornea that has undergone radial keratotomy appears to adjust constantly to changing environmental oxygen concentration, producing a new refractive error over a period of 24 hours or more. Additional study is required to identify with certainty the specific origin of the hyperopic shift at high altitude.

Acquired Hyperopia with Choroidal Folds

Six healthy adults suddenly developed a unilateral or bilateral hyperopic shift in refractive error of up to 6 diopters. Fundi of affected eyes showed typical choroidal folds. Visual acuity was improved to normal or near normal by plus lenses, and refraction and fundus appearance have remained stable for up to 23 years. The benign syndrome of acquired hyperopia with choroidal folds deserves emphasis in order to spare patients from unnecessary and potentially hazardous neurosurgical or orbital investigation.

THE AGEING EYE

ABSTRACTMost of the changes of vision due to ageing are attributable to changes in the crystalline lens. Hardening of the crystalline lens decreases the eye's ability to focus for near vision and so “reading” or “intermediate” glasses become necessary. Flattening of the crystalline lens causes a hyperopic shift in refractive error in the over 40 age group.Pathological conditions such as cataract, glaucoma and retinal degeneration can impair visual performance. Older persons need stronger and more carefully arranged lighting.