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Biomedical subjects

M G Davidson

Publications and source records attributed to M G Davidson.

At least 19 recordsLinked to original sources

Transpupillary diode laser retinopexy in dogs: ophthalmoscopic, fluorescein angiographic and histopathologic study.

OBJECTIVE: To evaluate the ophthalmoscopic, fluorescein angiographic and light microscopic effects of diode laser retinopexy application in the tapetal and nontapetal fundus in the dog, and to ascertain appropriate laser power settings for production of photocoagulative lesions in these two regions. ANIMALS STUDIED: Three adult female Beagle dogs. PROCEDURES: Laser burns were applied to selected areas in the fundus with an indirect headset delivery system using settings varying from 100 to 200 milliWatts (mW) and from 100 to 600 milliSeconds (mS) with total delivered energy ranging between 15 and 100 milliJoules (mJ). The dogs were then monitored by ophthalmoscopic examination and fluorescein angiography at regular intervals for 7-28 days. Histopathologic studies were performed at 7, 14 and 28 days after laser application. RESULTS: The diode laser produced ophthalmoscopically visible lesions in the nontapetal fundus with all laser settings used, and the appearance of these lesions corresponded to the energy levels used, and degree of pigment in the lased region. Gray-white colored lesions with minimal subsensory retinal edema were seen with settings as low as 100 mWatts/150 mSeconds. In the tapetal fundus, laser burns were more difficult to produce, less repeatable, and required higher energy levels. Laser burns appeared as bronze, dark green or black discolorations of the tapetum with varying degrees of subsensory retinal edema. Lesions were more reproducible and were achieved with lower settings in the tapetal area of the tapetal/nontapetal junction. Ophthalmoscopically, depigmentation and repigmentation of the RPE (nontapetal fundus) and degenerative changes in the overlying retina (tapetal fundus) developed in the laser burns over the 28-day study period. Fluorescein angiographic studies showed disruption of the blood-retinal barrier at the level of the RPE and fluorescein leakage into the subsensory retinal space was seen in most lesions at 24 h, was minimal at 3 days, and had resolved by 7 days. Histologically, grayish-white lesions in the nontapetal fundus, and bronze to small black lesions in the tapetal fundus were typically characterized by outer retinal necrosis and RPE migration. Gliosis was considered minimal, was confined to the retina, and no inflammatory cells were seen. Peripheral intense white lesions (nontapetum) and lesions with a black center (tapetal fundus) were characterized by more extensive panretinal and choroidal necrosis. Most of the nontapetal lesions and a few in the tapetal fundus showed the formation of a central retinal detachment. CONCLUSIONS: The diode laser effectively produces lesions suitable for retinopexy in both the nontapetal, pigmented fundus and the tapetal fundus, although variably so in the latter region. Initial laser settings of 100-150 mW/200 mS for the pigmented fundus, and 150 mW/200-300 mS for the peripheral tapetal fundus are recommended, and the clinician should gradually increase time interval settings to achieve a grayish-white lesion in the nontapetum, and a bronze to slightly black lesion in the tapetal fundus. If possible, retinopexy should be applied to the peripheral tapetal area or tapetal/nontapetal junction.

Angiography↗

Superficial, nonhealing corneal ulcers in horses: 23 cases (1989-2003).

OBJECTIVE: To characterize superficial, nonhealing corneal ulcers in the horse and to assess the affect of age, breed, sex, inciting cause of the ulcer, and treatment on healing time of these ulcers. DESIGN: Retrospective study. ANIMALS: Twenty-three horses with superficial, nonhealing corneal ulcerations. PROCEDURE: Medical records from 1989 to 2003 of horses diagnosed with superficial, nonhealing corneal ulcers were reviewed. Signalment, duration of clinical signs, ophthalmic abnormalities, treatment and response to treatment were recorded. Horses were treated, in addition to medical therapy, using debridement, debridement and grid keratotomy, superficial keratectomy, and superficial keratectomy with conjunctival graft placement. RESULTS: Mean age +/- SD of horses was 13.7 +/- 5.8 years. The mean time of presence of the corneal ulceration was 38.9 +/- 21.3 days. Mean time to complete re-epithelialization of the corneal ulcers after treatment was 20 +/- 14.7 days. Horses treated with debridement alone, grid keratotomy and superficial keratectomy healed in a mean time of 15.3 +/- 14.6 days, 16 +/- 12.6 days, and 22.8 +/- 6.7 days, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Horses treated with a single debridement at initial evaluation healed in a significantly shorter time period than horses treated with grid keratotomy or superficial keratectomy. The latter two procedures may be beneficial in the treatment of nonhealing ulceration in horses, but the results of this study suggest that these procedures should only be performed following failure of the ulcer to heal after epithelial debridement.

Animals↗

Bartonella vinsonii subspecies berkhoffi as a possible cause of anterior uveitis and choroiditis in a dog.

A 2-year old, neutered, female spaniel mixed breed was referred to the North Carolina State University Veterinary Teaching Hospital for evaluation of bilateral anterior uveitis. The dog was febrile and, in addition to anterior uveitis, multifocal hyporeflective lesions were present in the tapetal fundus of both eyes. The antibody titer for Bartonella vinsonii subspecies berkhoffi was positive (1 : 512). Aqueous paracentesis was performed for PCR in an attempt to detect B. vinsonii in the eye but was unsuccessful. The ocular manifestations of Bartonella infection in humans are currently expanding as more sensitive serologic and PCR techniques are being developed to identify Bartonella spp. In addition to optic neuritis and neuroretinitis, retinochoroidal lesions are one of the most common manifestations of B. henselae infection, and are frequently accompanied by vitreous or anterior segment inflammation. Diagnosis of a Bartonella infection in humans can be made on serology alone, in conjunction with ocular examination findings. The ultimate proof of B. vinsonii (berkhoffi) as a direct cause of ocular disease would be detection of the infectious agent in the eye. However, it is unknown at this time whether Bartonella causes ocular disease primarily, secondarily via an autoimmune reaction, or both. Due to the difficulties associated with culture of Bartonella spp. and the limitations of PCR, serology is currently the most useful tool for screening dogs for possible Bartonella spp. infection. In the case presented here, even though the PCR was negative, the clinical signs of anterior uveitis and choroiditis might reasonably be associated with B. vinsonii (berkhoffi) seroreactivity, which was repeatable on three separate occasions. Clinical improvement was also accompanied by a post-treatment decrease in B. vinsonii (berkhoffi) seroreactivity, potentially supporting resolution of Bartonella infection in this dog. This is the first reported case of a possible association between uveitis, choroiditis and Bartonella infection in the dog, without clinical manifestations of other organ or tissue involvement. Future studies based on PCR analysis of intraocular fluids may clarify the involvement of B. vinsonii (berkhoffi) in dogs with intraocular inflammatory disease. Furthermore, performing fluorescein angiography in dogs with elevated Bartonella titers may also prove useful in the identification and characterization of lesions.

Animals↗

Postnatal development of corneal curvature and thickness in the cat.

OBJECTIVE: To evaluate the postnatal development of central corneal curvature and thickness in the domestic cat. Animals studied Six Domestic Short-haired (DSH) kittens starting at 9 weeks of age and 6 adult cats. PROCEDURES: Kittens were evaluated biweekly to monthly for a 12-month period, starting at age 9 weeks. Corneal development was monitored by hand-held keratometry and ultrasound biomicroscopy. Standard regression analysis using a nonlinear least squares method was used to generate a formula that would predict corneal curvature as a function of age. RESULTS: Mean keratometry (K) values for the 9-week-old cats were 54.51 (+/-1.02) diopters (D) and these values steeply declined over the next 3 months to 44.95 (+/-0.90) D. Thereafter, K-values gradually decreased to reach a plateau by 12-15 months of age of 39.90 (+/-0.42) D. Because K-values still appeared to be slightly diminishing at this point, six other > 2-year-old cats were evaluated by keratometry and were found to have K-values of 38.99 (+/-0.81). Two to four diopters of astigmatism was common in young kittens whereas adult cats had a low mean degree of astigmatism (< 1 D). A formula that predicted keratometry values in diopters (K) as a function of age in weeks (w) was established as follows: K = 39.83 + 26.87 exp(-0.074 w). The central cornea increased in thickness primarily during the first 4 months of life with 9 week-old kittens having values of 0.379 (+/-0.012) mm; 16-week-old kittens, 0.548 (+/-0.021) mm and 67 week-old cats, 0.567 (+/-0.012) mm. CONCLUSIONS: The maturation process of the feline cornea proceeds over the first 1-2 years of life to attain an adult status that is characterized by a roughly spherical state of approximately 39 D corneal curvature, substantially flatter than the human cornea, and a central thickness similar to the human cornea. Research studies of the refractive or optical properties of the cornea in which cats are used as experimental animals should be conducted on animals greater than 18 months of age.

Animals↗

Acute vision loss after general anesthesia in a cat.

A 6-year-old, male castrated, domestic shorthair cat presented with a 2-week history of blindness following general anesthesia. Behavioral changes, lethargy, inappetence and neurological deficits were also noted. Ophthalmic evaluation revealed blindness, normal pupillary light response and dazzle response, but no other abnormalities. Serodiagnostic testing for common infectious agents was negative and a cerebrospinal fluid analysis was normal. History and postmortem examination following euthanasia revealed cerebrocortical necrosis most consistent with anesthesia related hypoxia.

Acute Disease↗

Use of an intravitreal sustained-release cyclosporine delivery device for treatment of equine recurrent uveitis.

OBJECTIVE: To evaluate the use of an intravitreal sustained-release cyclosporine (CsA) delivery device for treatment of horses with naturally occurring recurrent uveitis. ANIMALS: 16 horses with recurrent uveitis. PROCEDURES: Horses with frequent recurrent episodes of uveitis or with disease that was progressing despite appropriate medication were selected for this study. Additional inclusion criteria included adequate retinal function as determined by use of electroretinography, lack of severe cataract formation, and no vision-threatening ocular complications (eg, retinal detachment, severe retinal degeneration, and posterior synechia). Sustained-release CsA delivery devices (4 microg of CsA/d) were implanted into the vitreous through a sclerotomy at the pars plana. Reexaminations were performed 1, 3, 6, and 12 months after implantation, then continued annually. Ophthalmic changes, number of recurrent episodes of uveitis, and vision were recorded. RESULTS: The rate of recurrent episodes after device implantation (0.36 episodes/y) was less than prior to surgery (75 episodes/y). In addition, only 3 horses developed episodes of recurrent uveitis after surgery. Vision was detected in 14 of 16 affected eyes at a mean follow-up time of 13.8 months (range, 6 to 24 months). CONCLUSIONS AND CLINICAL RELEVANCE: This intravitreal sustained-release CsA delivery device may be a safe and important tool for long-term treatment of horses with chronic recurrent uveitis.

Animals↗

Ocular lesions associated with systemic hypertension in cats: 69 cases (1985-1998).

OBJECTIVE: To characterize clinical and clinicopathologic findings, response to treatment, and causes of systemic hypertension in cats with hypertensive retinopathy. DESIGN: Retrospective study. ANIMALS: 69 cats with hypertensive retinopathy. PROCEDURE: Medical records from cats with systemic hypertension and hypertensive retinopathy were reviewed. RESULTS: Most cats (68.1%) were referred because of vision loss; retinal detachment, hemorrhage, edema, and degeneration were common findings. Cardiac abnormalities were detected in 37 cats, and neurologic signs were detected in 20 cats. Hypertension was diagnosed concurrently with chronic renal failure (n = 22), hyperthyroidism (5), diabetes mellitus (2), and hyperaldosteronism (1). A clearly identifiable cause for hypertension was not detected in 38 cats; 26 of these cats had mild azotemia, and 12 did not have renal abnormalities. Amlodipine decreased blood pressure in 31 of 32 cats and improved ocular signs in 18 of 26 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Retinal lesions, caused predominantly by choroidal injury, are common in cats with hypertension. Primary hypertension in cats may be more common than currently recognized. Hypertension should be considered in older cats with acute onset of blindness; retinal edema, hemorrhage, or detachment; cardiac disease; or neurologic abnormalities. Cats with hypertension-induced ocular disease should be evaluated for renal failure, hyperthyroidism, diabetes mellitus, and cardiac abnormalities. Blood pressure measurements and funduscopic evaluations should be performed routinely in cats at risk for hypertension (preexisting renal disease, hyperthyroidism, and age > 10 years). Amlodipine is an effective antihypertensive agent in cats.

Animals↗

Ex vivo canine lens capsular sac explants.

BACKGROUND: Lens capsular sac explants from human cadaver eyes were used to investigate posterior capsular opacification (PCO). The purpose of this study was to characterize a similar model using canine tissue and to determine whether transferrin (Tf), transforming growth factor beta-2 (TGF-beta2), and insulin-like growth factor-1 (IGF-1) are secreted by lens epithelial cells (LEC) of these ex vivo sacs. METHODS: The lens from canine eyes was removed by extracapsular cataract extraction, the lens sac dissected free, pinned to a petri dish, and cultured in either serum-supplemented or serum-free medium. Morphologic characteristics and growth rate to confluence on the posterior capsule were studied by phase-contrast microscopy. Vimentin, alpha smooth muscle actin, and panTGF-beta expression by LEC were determined by immunohistochemistry. Tf, TGF-beta2, and IGF-1 levels were measured by ELISA in the supernatant of sacs cultured in serum-free medium. RESULTS: The mean time to confluence of LEC onto the posterior capsule was 5.4+/-1.1 days (n=22) and 14.7+/-3.7 days (n=14) for sacs in serum-supplemented and serum-free medium, respectively. Following development of confluence, explants displayed opacification and light scatter from cellular proliferation and capsular contraction. Confluent LEC expressed vimentin, alpha smooth muscle actin, and TGF-beta2, and both Tf and TGF-beta2 were secreted into the culture supernatant. CONCLUSION: Canine lens sac explants have characteristics virtually identical to those of human origin, and appear to be a useful alternative tissue source for this model when human cadaver eyes are unavailable. Tf and TGFbeta-2, but not IGF-1, are secreted by LEC in explanted lens sacs and may influence the proliferation and metaplasia of LEC during the development of PCO.

Actins↗

Toxoplasmosis.

Toxoplasmosis in dogs and cats can cause chorioretinitis, anterior uveitis, or both. Ocular lesions are a common manifestation of generalized toxoplasmosis. The prevalence of toxoplasmosis as a cause of idiopathic anterior uveitis in cats is not clear, although there is a significant association between exposure to T. gondii and feline anterior uveitis. The pathogenesis of ocular toxoplasmosis may be different in humans and cats, and the anterior uveitis may represent a type of immune-mediated inflammation. A diagnosis is made by observing compatible clinical findings and obtaining supportive findings on serologic tests. Despite improved diagnostic techniques, including determination of IgM class antibodies and PCR testing, definitive diagnosis of ocular toxoplasmosis remains a challenge. Topical anti-inflammatory therapy should be used in cats with anterior uveitis, a positive serum titer, and no concurrent systemic signs. Systemic clindamycin should be given to cats with ocular and systemic signs and to cats with suggestive serology and idiopathic anterior uveitis that fails to respond to topical therapy alone.

Animals↗

Effect of surgical technique on in vitro posterior capsule opacification.

PURPOSE: To compare the effect of different cataract extraction surgical techniques on residual lens epithelial cell (LEC) density and cell regrowth rates using an in vitro model of posterior capsule opacification (PCO). SETTING: Comparative Ophthalmology Research Laboratories, North Carolina State University, Raleigh, North Carolina, USA. METHODS: Lens capsule explants were prepared from freshly enucleated canine globes after extracapsular cataract extraction (ECCE), phacoemulsification, or phacoemulsification followed by capsule vacuuming. Initial cell density on the capsule and cell proliferation were determined by phase contrast microscopy. The effects of the surgical technique on time to confluent growth of the cells across the posterior lens capsule were determined. RESULTS: Residual cell density on the remaining anterior capsule immediately after lens removal was 31.6% +/- 19.3%, 16.1% +/- 8.9%, and 7.7% +/- 5.7% in the ECCE, phacoemulsification, and phacoemulsification/capsule-vacuuming groups, respectively. Time to confluence (range 5.0 to 6.3 days) was not significantly different among the 3 groups when the lens capsules were cultured in serum-supplemented media. The confluence rate was significantly longer (by approximately 5 to 7 days) in the phacoemulsification/capsule-vacuuming group than in the other 2 groups when the capsules were cultured in serum-free media. CONCLUSIONS: Phacoemulsification with and without anterior and equatorial capsular vacuuming led to less initial LEC density in the capsular bag than ECCE. However, because cell proliferation rates among the 3 groups were only marginally affected, near 100% removal of LEC at the time of cataract extraction may be necessary to prevent PCO.

Animals↗

Histologic and immunohistochemical characterization of lens capsular plaques in dogs with cataracts.

OBJECTIVE: To determine histologic and immunohistochemical characteristics of the multifocal adherent plaques that commonly develop on the internal surfaces of the anterior and posterior lens capsules in dogs with cataracts. SAMPLE POPULATION: 31 anterior and 4 posterior capsular specimens collected during lens extraction surgery in dogs with cataracts. PROCEDURE: Specimens were evaluated, using light and transmission electron microscopy. Immunohistochemical techniques were used to localize cytokeratin, vimentin, alpha-smooth muscle-specific actin, fibronectin, tenascin, and transforming growth factor-beta (TGF-beta) within plaques. RESULTS: Histologically, plaques comprised elongated spindle-shaped cells that formed a placoid mass. Cells were embedded in an extracellular matrix containing collagen fibrils, often with duplicated or split basement membranes. Immunohistochemically, normal lens epithelial cells and cells within plaques stained for vimentin. Most cells and some areas of the extracellular matrix within plaques stained for TGF-beta and alpha-smooth muscle-specific actin. Fibronectin and tenascin were also detected in the extracellular matrix. CONCLUSIONS AND CLINICAL RELEVANCE: Canine lens capsular plaques are histologically and immunohistochemically similar to posterior capsule opacification and subcapsular cataracts in humans, which suggests that the canine condition, like the human conditions, is associated with fibrous metaplasia of lens epithelial cells. Transforming growth factor-beta may play a role in the genesis of capsular plaques. Because severity of plaques was correlated with stage of cataract development, earlier surgical removal of cataracts may be useful to avoid complications associated with plaque formation.

Actins↗

Telomerase activity in lens epithelial cells of normal and cataractous lenses.

Telomerase is a ribonucleoprotein responsible for maintaining telomere length, preventing chromosomal degradation and recombination, and repairing DNA strand breaks. These activities are believed to be important in preventing cell senescence. Telomerase activity is normally found in germinal, neoplastic and stem cells, but not any ocular tissue studied to date. The epithelium of the crystalline lens is comprised of a population of cells with diverse mitotic potential including the germinative epithelium which contains cells with the potential for unlimited replicative capacity, equatorial cells which terminally differentiate into lens fibers, and the central epithelium which are considered to be quiescent and nonreplicative under normal circumstances. We speculated that the germinative region of lens epithelial cells might have telomerase activity, and that dysregulation of its activity might be associated with cataractogenesis. We investigated these hypotheses in lens capsule specimens from normal and cataractous dogs and from cultures of canine lens epithelial cells using standard assays for telomerase activity and telomere length. Telomerase activity was found in normal canine lens epithelial cells in the central, germinative and equatorial regions of the anterior lens capsule at equivalent levels. Similar findings were made in feline and murine lens epithelial cells, indicating that the presence of telomerase activity in the lens was not species specific. Lens fiber cells, corneal epithelium and endothelium and nonpigmented ciliary epithelium were telomerase negative. Telomerase activity and telomere lengths were significantly greater in lens epithelia from cataractous lenses when compared with normal lenses. Since telomerase activity is associated with an immortal phenotype, the presence of telomerase activity in the lens epithelial cells may function to prevent conversion to senescence. It was, therefore, difficult to explain why these cells cannot be passaged more than four times in culture. We found that telomerase activity and telomere lengths gradually decreased with increased passages until telomerase activity was no longer present at passage two. Consistent with these findings, there were no senescent cells present on the lens capsule when the lens was initially dissected for culture, but an increasing number of cells were senescent with each passage, correlating well with the loss of telomerase activity. Telomerase activity is likely important in the germinative epithelium to maintain its proliferative potential and prevent cell senescence. Telomerase may function in the quiescent, central lens to maintain telomeres damaged by oxidative stress and ultraviolet light exposure, thereby preventing accelerated loss of these elements which triggers cell senescence. It remains to be determined if the increase in telomerase activity in lens epithelial cells from cataractous lenses is a primary dysregulation that may have a role in the development of the cataract, or is secondary to cataract formation.

Animals↗

Low-dose oral administration of interferon-alpha for the treatment of immune-mediated keratoconjunctivitis sicca in dogs.

This preliminary study was designed to evaluate the effectiveness and dosage of oral use of interferon-alpha (IFN-alpha) in the treatment of naturally occurring, immune-mediated, canine keratoconjunctivitis sicca (KCS). Dogs with chronic immune-mediated KCS were selected from the two clinic populations. All medication, except topical artificial tears, was discontinued at least 2 weeks prior to beginning the clinical trial. IFN-alpha was administered orally once daily to the dogs by their owners as the sole therapy for the KCS. Examinations of the dogs were performed every 2 weeks for the duration of the trial (12 weeks). Each dog was given either two or three separate, escalating doses (20, 40, 80 IU of the IFN-alpha. A favorable response was observed in 55% (11/20) of all dogs treated. Clinical findings of those dogs that responded included increased wetting of the eyes, decreased mucus discharge, and fewer signs of discomfort. There was a nearly significant difference (p = 0.08) in pretreatment mean Schirmer's tear test (STT) between the dogs that responded (6.4 +/- SEM 0.62 mm/min) and those that did not respond (4.7 +/- SEM 0.69 mm/min) to the orally administered IFN-alpha. Seven of 11 dogs with favorable outcomes had an increased STT of at least 5 mm/min after treatment with oral IFN-alpha and the group had a post-treatment STT (10.5 +/- SEM 1.4 mm/min) significantly greater than baseline (p = 0.0004). The post-treatment STT of the dogs that did respond was significantly greater (p < 0.01) than the post-treatment mean STT of dogs that did not respond. All dogs that responded did so with the 20 or 40 IU dose of IFN-alpha. No side effects were noted and all dogs tolerated the treatment well.

Administration, Oral↗

Efficacy of doxycycline, azithromycin, or trovafloxacin for treatment of experimental Rocky Mountain spotted fever in dogs.

Dogs were experimentally inoculated with Rickettsia rickettsii (canine origin) in order to compare the efficacies of azithromycin and trovafloxacin to that of the current antibiotic standard, doxycycline, for the treatment of Rocky Mountain spotted fever. Clinicopathologic parameters, isolation of rickettsiae in tissue culture, and PCR amplification of rickettsial DNA were used to evaluate the response to therapy or duration of illness (untreated infection control group) in the four groups. Concentrations of the three antibiotics in plasma and blood cells were measured by high-performance liquid chromatography. Doxycycline and trovafloxacin treatments resulted in more-rapid defervescence, whereas all three antibiotics caused rapid improvement in attitudinal scores, blood platelet numbers, and the albumin/total-protein ratio. Based upon detection of retinal vascular lesions by fluorescein angiography, trovafloxacin and doxycycline substantially decreased rickettsia-induced vascular injury to the eye, whereas the number of ocular lesions in the azithromycin group did not differ from that in the infection control group. As assessed by tissue culture isolation, doxycycline resulted in the earliest apparent clearance of viable circulating rickettsiae; however, rickettsial DNA could still be detected in the blood of some dogs from all four groups on day 21 postinfection, despite our inability to isolate viable rickettsiae at that point. As administered in this study, trovafloxacin was as efficacious as doxycycline but azithromycin proved less efficacious, possibly due to the short duration of administration.

Animals↗

Retinal degeneration associated with vitamin E deficiency in hunting dogs.

A group of Walker Hounds and Beagles that were fed a diet of table scraps were examined because of slow, progressive loss of vision. Clinical and microscopic features of the disease were correlated to the dogs' micronutrient status. Sensory retinal degeneration, predominantly in the central tapetal fundus, was found in all dogs, and severity of changes varied with age of the dog. Plasma, serum, and tissue concentrations of vitamin E were low in affected dogs (10 to 40% of control values). Lipofuscin accumulation was found on microscopic examination in retinal pigment epithelium, smooth muscle cells of the intestinal tract, and neurons of the CNS. Findings were consistent with nutritional vitamin E deficiency and oxidative injury to photoreceptors of the retina. Changes in these dogs were similar to those described for central progressive retinal atrophy and equine lower motor neuron disease, suggesting these diseases may share a common pathogenesis to vitamin E deficiency.

Age Factors↗