Quality of life and functional vision concerns of children with cataracts and their parents.

PurposeTo identify specific health-related quality of life (HRQOL) and functional vision concerns affecting children with cataracts and common associated conditions as expressed by children or one of their parents (proxy), and HRQOL concerns affecting the parents themselves.MethodsIndividual semi-structured interviews were conducted with parents of children with cataracts (N=31) and with the children themselves (ages 5-17 years; N=16). Transcripts of recorded interviews were evaluated using NVivo software. Specific concerns were identified and coded, and broad themes were identified. The frequency of each theme was calculated, with the frequency of specific concerns within each theme.ResultsRegarding the child's experience, 6 themes were identified: Visual Function (mentioned by 16 of 16 children (100%) and by 26 of 31 parents (84%), Social (94 and 65%), Treatment (81 and 90%), Worry (75 and 10%), Emotions (63 and 68%), and Physical Discomfort (63 and 26%). Worry showed the largest discrepancy between child and their parent; although 75% children reported Worry, only 6% of parents reported that their child experienced Worry (P=0.0009). Regarding the parents' own experience, 5 themes were identified: Worry (100%), Compensation for Condition (100%), Treatment (94%), Emotions (90%), and Affects Family (52%).ConclusionsA wide range of concerns were identified from interviews of children with cataracts and their parents. Concerns reflect the impact of cataracts in physical, emotional, and social domains, and specific concerns will be used for the development of questionnaires to quantify the quality of life and functional vision effects of cataracts.

Is intermittent exotropia a curable condition?

Surgical treatment of childhood intermittent exotropia (XT) is associated with high recurrence rates. In addition, the natural history of intermittent XT has not been rigorously studied and, anecdotally, some cases resolve without surgery. We compared long-term cure rates in children with surgically and non-surgically managed intermittent XT. Children undergoing surgery for intermittent XT who had 5 years follow-up were retrospectively identified. A non-surgical cohort of comparable children was selected by matching each surgical patient for age at onset and age at the 5-year examination. Cure was defined as no manifest tropia on examination or by history, no new monofixation (stereoacuity subnormal for age), and no additional surgery. Each group had 33 children (total follow-up from presentation 7.2±2.6 years in the surgical group vs 6.8±2.3 years). There were no significant differences between groups for age at onset, age at presentation, or distance or near angle of deviation at presentation (all P≥0.4). The cure rate at 5 years was 30% in the surgical group and 12% in the non-surgical group (P=0.1; difference 18%, 95% CI -1 to 37%). Only a small proportion of surgical and non-surgical patients met our definition of cure, with the vast majority demonstrating a constant or intermittent manifest deviation after an average of 7 years follow-up. In childhood intermittent XT, long-term cure is difficult to achieve with surgical intervention, and in some patients managed non-surgically the intermittent XT will spontaneously resolve.

Initial treatment outcomes in chronic sixth nerve palsy.

INTRODUCTION: We conducted a prospective multi-center, nonrandomized, data-collection study of patients with chronic sixth cranial nerve palsy. We evaluated success rates with conservative nonsurgical management, botulinum toxin (botox) treatment, strabismus surgery, and a combination of botox treatment and surgery. METHODS: All members of the American Association for Pediatric Ophthalmology and Strabismus and the North American Neuro-Ophthalmology Society were invited to enroll patients with sixth nerve palsy or paresis of more than 6 months duration over a 2-year period (between March 1998 and February 2000). The botox and surgical groups received intervention within 3 months of enrollment. Success at 6 months from enrollment was defined as absence of diplopia in primary position and no more than 10 prism diopters (pd) distance esotropia in primary position. Patients with no follow-up were excluded. RESULTS: Fifty-six eligible patients were enrolled by 33 investigators. Eighteen (32%) were traumatic in etiology, 15 (27%) were unknown (including presumed hypertensive), 14 (25%) were neoplastic, 2 (4%) were diabetic, and 7 (13%) were other. Twenty (35%) were managed conservatively without surgery, 10 (18%) with botox treatment, 19 (33%) with surgery, and 8 (14%) with a combination of botox treatment and surgery. Success at 6 months from enrollment was 15% in the conservatively managed cases, 10% with botox alone, 39% with surgery alone, and 25% with a combination of botox and surgery. CONCLUSIONS: This study demonstrates that management of chronic sixth nerve palsy and paresis remains challenging. Spontaneous recovery occurs but is uncommon. Botox treatment alone was rarely successful, and a single surgical procedure had a lower-than-expected success rate. Care should be taken in directly comparing success rates between treatment groups because of bias in patient selection.

The amblyopia treatment study visual acuity testing protocol.

OBJECTIVE: To evaluate the reliability of a new visual acuity testing protocol for children using isolated surrounded HOTV optotypes. METHODS: After initial pilot testing and modification, the protocol was evaluated using the Baylor-Video Acuity Tester (BVAT) to present isolated surrounded HOTV optotypes. At 6 sites, the protocol was evaluated for testability in 178 children aged 2 to 7 years and for reliability in a subset of 88 children. Twenty-eight percent of the 178 children were classified as having amblyopia. RESULTS: Using the modified protocol, testability ranged from 24% in 2-year-olds to 96% in 5- to 7-year-olds. Test-retest reliability was high (r = 0.82), with 93% of retest scores within 0.1 logMAR unit of the initial test score. The 95% confidence interval for an acuity score was calculated to be the score +/-0.125 logMAR unit. For a change between 2 acuity scores, the 95% confidence interval was the difference +/-0.18 logMAR unit. CONCLUSIONS: The visual acuity protocol had a high level of testability in 3- to 7-year-olds and excellent test-retest reliability. The protocol has been incorporated into the multicenter Amblyopia Treatment Study and has wide potential application for standardizing visual acuity testing in children.

Predictors of nonrecovery in acute traumatic sixth nerve palsy and paresis.

PURPOSE: To evaluate whether nonrecovery from acute traumatic sixth nerve palsy could be predicted from demographic factors or palsy characteristics. DESIGN: Prospective, observational case series SETTING: Multicenter (academic and private practices). OUTCOME MEASURE: Nonrecovery, defined as the presence of diplopia in primary position or more than 10 prism diopters of distance esotropia in primary position at 6 months after onset. METHODS: Using data from a previously described cohort of 84 eligible patients with acute traumatic sixth nerve palsy, we performed multivariate analyses of demographic factors and palsy characteristics. RESULTS: Nonrecovery at 6 months after onset was associated with a complete palsy (adjusted risk ratio, 9.11; 95% confidence interval [CI], 2.77-14.84) and with a bilateral palsy or paresis (adjusted risk ratio, 2.53; 95% CI, 0.98-4.29). The choice of conservative management (observation, prism, or patch) versus acute injection of Botulinum toxin (within 3 months of injury) did not influence final recovery. CONCLUSIONS: In acute traumatic sixth nerve palsy or paresis, failure to recover by 6 months after onset was associated independently with inability to abduct past midline at presentation and bilaterality. Although the overall recovery rate is high in acute traumatic sixth nerve palsy or paresis, a complete or bilateral case has a poor prognosis and is more likely to need strabismus surgery.

Photographic and clinical techniques for outcome assessment in sixth nerve palsy.

PURPOSE: There are few data on the reproducibility of clinical assessment of ductions and alignment. We evaluated photographic methods that may be used for masked outcome determination in a clinical trial and compared them with clinical measures. DESIGN: Interexaminer reliability study. PARTICIPANTS: Twenty-three patients with unilateral sixth nerve palsy and three control participants were clinically evaluated by two masked examiners. MAIN OUTCOME MEASURES: Abduction deficit was graded as 0 to -5. Simultaneous prism and cover tests (SPCT) and alternate cover tests (ACT) were performed at distance and near fixation. Photographs were taken of abduction and distance alignment by each examiner. The photographs were evaluated by a third masked reader, who assigned abduction grade, measured absolute abduction (mm) and relative abduction (%), and calculated alignment in prism diopters (pd). Agreement was evaluated by calculating intraclass correlation coefficients (r(i)), weighted kappa statistics (kappa), and Spearman rank correlation coefficients (r(S)). RESULTS: There was excellent agreement between the two clinicians in clinical abduction deficit (kappa = 0.86) SPCT and ACT at distance and near (r(i) 0.94-0.96), between the clinical grade and masked photographic grade (kappa = 0.83), and between the two sets of photographs for absolute abduction and relative abduction (r(i) = 0.98 and 0.97). Both photographic measures of abduction correlated well with the clinical grade (r(S) = -0.96 for each). Measurements of alignment from photographs correlated with clinical SPCT measurement (r(i) = 0.88), but had a lower level of absolute agreement (38% within 5 pd) than between two independent SPCT measurements (96% within 5 pd). CONCLUSIONS: The excellent interexaminer agreement of our new photographic abduction assessment and of masked clinical measures suggest that these methods would be useful in clinical trials. In contrast, our simple method of photographic assessment of alignment lacks excellent agreement with the clinical assessment. These data are important in planning clinical trials in strabismus.

Postnatal growth retardation exacerbates acidosis-induced retinopathy in the neonatal rat.

PURPOSE: We have previously described a metabolic acidosis-induced retinopathy in the neonatal rat, similar to retinopathy of prematurity (ROP). We also have reported exacerbation of oxygen-induced retinopathy by postnatal growth retardation, produced by raising newborn rats in 'expanded' litters. In the present study, we investigated the effect of postnatal growth retardation on the incidence and severity of acidosis-induced retinopathy. METHODS: 100 newborn Sprague-Dawley rats were randomly assigned to two expanded litters of 25 pups each and five standard control litters of 10 pups each. All rats were gavaged with 10 mM/kg NH(4)Cl twice daily from days two to seven. Following five days of recovery, retinal vasculature was assessed using ADPase staining, light microscopy, and computer-assisted image analysis. The presence of neovascularization (NV), severity of NV (clock hours), and vascularized retinal areas, were evaluated in a masked manner. RESULTS: NV occurred in 52% of rats in expanded litters versus 18% of rats in standard control litters (p = 0.005). Postnatal growth retardation of pups in expanded litters was confirmed by comparing total body weight of pups raised in expanded and standard control litters (10.8g vs 13.4g on day 8, p < 0.001; 20.8g vs 25.2g on day 13, p = 0.002). CONCLUSIONS: Postnatal growth retardation increases the incidence of acidosis-induced retinopathy in the neonatal rat. Our study provides further evidence that postnatal growth retardation is a risk factor for preretinal neovascularization in immature retinae and is consistent with the clinical observation that the smallest and sickest premature infants are more likely to suffer from ROP.

Preretinal neovascularization associated with acetazolamide-induced systemic acidosis in the neonatal rat.

PURPOSE: NH4Cl gavage in the neonatal rat produces a metabolic acidosis-induced retinopathy which serves as a model for retinopathy of prematurity (ROP). Acetazolamide induces a metabolic acidosis via an alternative biochemical mechanism (bicarbonate loss versus hydrogen ion load). In the present study, the following hypothesis was tested: acetazolamide-induced acidosis is associated with preretinal neovascularization in the neonatal rat. METHODS: All studies used newborn Sprague-Dawley rats raised in expanded litters of 25. Arterial blood pH was measured to determine the level of acidosis induced by intraperitoneal (IP) acetazolamide (50 or 200 mg/kg) or saline. In a separate retinopathy study, newborn rats (n = 75) were randomized to either IP acetazolamide, 50 mg/kg (low-dose), or IP saline twice daily from days 2 to 7. After 5 days of recovery, retinal vasculature was assessed using ADPase staining and light microscopy. The presence and severity (clock hours) of neovascularization were assessed by three masked observers. In an additional retinopathy study, newborn rats (n = 100) were randomized to either IP acetazolamide, 200 mg/kg (high-dose), or IP saline twice daily from days 2 to 7. After 5 days of recovery, the retinas were similarly analyzed. RESULTS: Neovascularization occurred in 59% of rats receiving high-dose acetazolamide (200 mg/kg). High-dose acetazolamide produced a severe acidosis (pH 7.13 +/- 0.06) during drug delivery. Low-dose acetazolamide (50 mg/kg) produced a pH (7.22 +/- 0.07) that was intermediate between high-dose (200 mg/kg) acetazolamide (P < 0.001) and saline controls (7.42 +/- 0.06, P < 0.001); however, neither low-dose acetazolamide nor saline induced preretinal neovascularization. CONCLUSIONS: Acidosis induced by high-dose acetazolamide, independent of hyperoxemia or hypoxemia, is associated with preretinal neovascularization in the neonatal rat. Induction of neovascularization appears to depend on a critical threshold of acidosis severity. This study further supports a proposed independent role for acidosis in the pathogenesis of ROP.

Botulinum toxin treatment versus conservative management in acute traumatic sixth nerve palsy or paresis.

PURPOSE: Botulinum toxin (BTX), injected into the ipsilateral medial rectus muscle, has been advocated for the management of acute traumatic sixth nerve palsy or paresis. We conducted a multicenter, nonrandomized, data collection study to evaluate recovery rates of patients treated with either conservative measures or BTX. METHODS: All members of the American Association for Pediatric Ophthalmology and Strabismus and the North American Neuro-Ophthalmology Society were invited to enroll patients with acute traumatic sixth nerve palsy or paresis during a 2-year period (between March 1996 and February 1998). The BTX group was defined as patients who received a BTX injection within 3 months of injury. Recovery at 6 months from injury was defined as absence of diplopia in the primary position and a distance esotropia of no more than 10 PD in the primary position. Nonrecovered patients with less than 6 months of follow-up (n = 15) were excluded. RESULTS: Eighty-four eligible patients were enrolled by 46 investigators. Sixty-two patients (74%) were treated conservatively and 22 (26%) with BTX. Sixty-two patients (74%) had unilateral palsy, and 22 (26%) had bilateral palsy. Recovery rates were similar between BTX and conservatively treated patients (overall: 73% vs 71%, P = 1.0; unilateral: 81% vs 83%, P = 1.0; bilateral: 50% vs 38%, P = 0.66, respectively). CONCLUSIONS: In this prospective multicenter study of acute traumatic sixth nerve palsy or paresis, patients treated with either BTX or conservative measures had similar high recovery rates.

Neovascularization grading methods in a rat model of retinopathy of prematurity.

PURPOSE: The method of counting cell nuclei above the internal limiting membrane in histologic sections is considered the standard when quantifying neovascularization (NV) in rodent oxygen-induced retinopathy (OIR). An alternative, more rapid method of counting clock hours in flatmounted adenosine diphosphatase (ADPase)-stained rat retinas is analogous to clinically scoring retinopathy of prematurity (ROP). In the present study, the validity of counting clock hours was evaluated by a direct comparison of these techniques. The intereye correlation of NV score and retinal vascular area were also studied. METHODS: Newborn Sprague-Dawley rats were exposed to cycles of O2 (80-10%) for 7 days, followed by 5 days of room air recovery. Preretinal NV was quantified by three masked observers counting clock hours in flatmounted ADPase-stained retinas of both eyes. Retinal vascular and total retinal areas were calculated using computer-assisted analysis. Representative retinas that had been scored positive (n = 10) and negative (n = 3) for NV and room air control retinas (n = 3) were embedded in paraffin. Each entire peripheral retinal quadrant was serially sectioned at 6 microm and stained with hematoxylin and eosin. Nuclei above the internal limiting membrane were then counted in a masked manner. The total number of nuclei counted per retina was defined as the nucleus count (704-938 sections per retina; 12,900 sections). Correlations were evaluated using Spearman rank coefficients. RESULTS: The nucleus count was 0 to 44 in room air control retinas, 0 to 40 in negative OIR retinas, and 250 to 5634 in positive OIR retinas. The nucleus count was highly correlated with the clock hour score (r(s) = 0.95, P = 0.0001). For the paired retinas, there was a significant correlation between right and left eyes in the severity of NV (clock hours; r(s) = 0.76, P = 0.0001) and the ratio of retinal vascular area to total retinal area (r(s) = 0.81, P = 0.0001). CONCLUSIONS: The more rapid method of counting clock hours in flatmounted ADPase-stained retinas is valid for quantifying NV in rat models of ROP. Incidence and severity of NV and vascularized areas were similar between left and right eyes, which permits the use of paired retinas for complementary research techniques.

Retinopathy associated with enterococcus enteropathy in the neonatal rat.

PURPOSE: Preretinal neovascularization has been previously observed in neonatal rats with spontaneously occurring diarrhea. This neovascularization appears analogous to retinopathy of prematurity (ROP), which occurs in human neonates. A new enterococcus species, designated Enterococcus rattus, has been isolated from the duodenum of these rats. In the present controlled study, the effect of the enteropathy induced by this organism on the retinal vasculature in the neonatal rat was further investigated. METHODS: One hundred fifty newborn Sprague-Dawley rats were randomly assigned to 6 expanded litters (n = 25). On the second day of life, animals were gavaged with either 100 microl of E. rattus suspension (1.0 X 10(7) colony forming units, inoculated group, n = 100 rats) or 100 microl saline (control group, n = 50 rats). All rats were raised in room air and were killed on day 13 of life. Duodenal and blood samples were cultured. The retinal vasculature was assessed using fluorescent microscopy and ADPase staining in a masked manner. Two additional inoculated litters and one control litter were studied for evaluation of arterial blood gases and validation of the grading method for preretinal neovascularization. RESULTS: One hundred percent of rats in the inoculated group developed severe diarrhea and had duodenal cultures positive for E. rattus compared with 0% in the control group. Preretinal neovascularization similar to ROP occurred in 55% of rats in the inoculated group compared with 2% in the control group (P = 0.001). Retinal vascular areas were reduced in the inoculated group (mean +/- SD, 89% +/- 5% versus 96% +/- 2%; P < 0.001). Rats in the inoculated group demonstrated severe growth retardation (final weight, 9.7 +/- 2.2 versus 16.7 +/- 2.7 g, P < 0.001). Inoculated animals also experienced acidosis (pH 7.31 +/- 0.06 versus 7.39 +/- 0.06 control, P = 0.04). CONCLUSIONS: A previously undescribed enterococcal enteropathy was associated with preretinal neovascularization similar to ROP in the neonatal rat. This supports an independent role for factors other than inspired oxygen in the development of ROP.

Metabolic acidosis-induced retinopathy in the neonatal rat.

PURPOSE: Carbon dioxide (CO2)-induced retinopathy (CDIR) in the neonatal rat, analogous to human retinopathy of prematurity (ROP), was previously described by our group. In this model, it is possible that CO2-associated acidosis provides a biochemical mechanism for CDIR. Therefore, the effect of pure metabolic acidosis on the developing retinal vasculature of the neonatal rat was investigated. METHODS: A preliminary study of arterial blood pH was performed to confirm acidosis in our model. In neonatal rats with preplaced left carotid artery catheters, acute blood gas samples were taken 1 to 24 hours after gavage with either NH4Cl 1 millimole/100 g body weight or saline. In the subsequent formal retinopathy study, 150 newborn Sprague-Dawley rats were raised in litters of 25 and randomly assigned to be gavaged twice daily with either NH4Cl 1 millimole/100 g body weight (n = 75) or saline (n = 75) from day 2 to day 7. After 5 days of recovery, rats were killed, and retinal vasculature was assessed using fluorescein perfusion and ADPase staining techniques. RESULTS: In the preliminary pH study, the minimum pH after NH4Cl gavage was 7.10+/-0.10 at 3 hours (versus 7.37+/-0.03 in controls, mean +/- SD, P < 0.01). In the formal retinopathy study, preretinal neovascularization occurred in 36% of acidotic rats versus 5% of controls (P < 0.001). Acidotic rats showed growth retardation (final weight 16.5+/-3.0 g versus 20.2+/-2.6 g, P < 0.001). The ratio of vascularized to total retinal area was smaller in acidotic rats (94%+/-4% versus 96%+/-2%, P < 0.001). CONCLUSIONS: Metabolic acidosis alone induces neovascularization similar to ROP in the neonatal rat. This suggests a possible biochemical mechanism by which high levels of CO2 induce neovascularization and supports the suggestion that acidosis may be an independent risk factor for ROP.

Carbon dioxide-induced retinopathy in the neonatal rat.

PURPOSE: Hypercarbia has been suggested as a risk factor for retinopathy of prematurity (ROP). We investigated the effect of hypercarbia on the retinal vasculature of the neonatal rat to determine whether hypercarbia alone could induce preretinal neovascularization analogous to ROP. METHODS: In a preliminary blood gas study, 8-11-day-old rats were exposed to specific levels of inspired O2 and either 0.2% CO2 or 10% CO2. Arterial blood gases were obtained, and a level of inspired O2 was determined that, when combined with inspired 10% CO2, would produce a PaO2 equivalent to room air (pure hypercarbia). In the formal retinopathy study, 300 newborn rats raised in 12 expanded litters (n = 25 each) were exposed for 7 days to either room air, 10% CO2 in 21% O2 and nitrogen (high-inspired CO2 group) or 10% CO2 in 12.5% O2 and nitrogen (pure-hypercarbia group). Each type of exposure was followed by recovery in room air for 5 days. Animals were sacrificed on day 13 and retinae were analyzed, using fluorescein perfusion and ADPase staining techniques. RESULTS: Neovascularization occurred in 19% of rats in the high-inspired CO2 group, and 14% of rats in the pure-hypercarbia group, compared to 0% of rats exposed to room air alone (p = 0.001, Chi square). CONCLUSIONS: In the neonatal rat model, exposure to hypercarbia alone, followed by room air recovery, results in preretinal neovascularization similar to that seen in oxygen-induced retinopathy. Our results support the suggestion that hypercarbia may be a risk factor for retinopathy of prematurity.

The effect of carbon dioxide on oxygen-induced retinopathy in the neonatal rat.

PURPOSE: Hypercarbia has been suggested as a risk factor for retinopathy of prematurity. We investigated the effect of raised inspired carbon dioxide on oxygen-induced retinopathy in the neonatal rat. METHODS: Newborn rats raised in expanded litters (n = 25 each) were exposed to cycles of hyperoxia (80% O2) and hypoxia (10% O2 for 7 days, followed by room air recovery for 5 days. During cyclic oxygen exposure, 3 litters (n = 75) were exposed to 10% CO2 (PaCO2 78 mm Hg +/- 6; mean +/- SD) and 3 litters (n = 75) were exposed to 0.2% CO2 (PaCO2 45 mm Hg +/- 7). Animals were sacrificed on day 13 and retinae were analyzed using fluorescein perfusion and ADPase staining techniques. RESULTS: Neovascularization occurred in 85% of rats exposed to high CO2 compared to 52% of rats exposed to low CO2 (p = 0.001). The severity of neovascularization, in clock hours, was also greater in the rats exposed to high CO2 (p < 0.001). CONCLUSIONS: Exposure to high CO2 results in an increased incidence and severity of neovascularization in a rat model for oxygen-induced retinopathy. Our results support the suggestion that hypercarbia may be a risk factor for retinopathy of prematurity.

The effect of raised inspired carbon dioxide on normal retinal vascular development in the neonatal rat.

PURPOSE: Raised arterial carbon dioxide levels have been suggested as a risk factor for retinopathy of prematurity (ROP). We investigated the effect of raised inspired CO2 on normal postnatal vasculogenesis in the neonatal rat retina. METHODS: One hundred fifty newborn rat pups were divided among 15 mothers (n = 10 for each litter). Five litters were exposed to low CO2 (0.2%), 5 litters exposed to 6%, and 5 litters to 10% CO2. On day 7 of life the rats were sacrificed and the total retinal and vascularized retinal areas analyzed. RESULTS: The vascularized retinal area and ratio of vascularized to total retinal area were reduced in rats exposed to 6% and 10% CO2. CONCLUSIONS: Raised inspired CO2 was associated with retardation of normal retinal vascular development and increased peripheral avascular area in neonatal rats. Raised CO2 may be a risk factor for the development of abnormal neovascularization such as in ROP.

Prostatic intraepithelial neoplasia and well differentiated adenocarcinoma maintain an intact basement membrane.

The status of the basement membrane in prostatic intraepithelial neoplasia (PIN) and adenocarcinoma is unsettled. Previous studies using antibodies directed against Type IV collagen have been hindered by intense staining around the stromal smooth muscle fibers, making interpretation of acinar staining difficult. We employed a monoclonal antibody to heparan sulfate proteoglycan (HSPG) to overcome this problem, recognizing that HSPG is present in the basement membrane of epithelial and endothelial cells, but not stromal smooth muscle cells. In 22 totally-embedded whole mount radical prostatectomies for adenocarcinoma which contained PIN, intense HSPG immunoreactivity was observed in the basement membrane of all normal and hyperplastic acini, 98% of acini with high grade PIN, and 100% of acini of well differentiated (Gleason score 5) adenocarcinoma; vessels served as the internal positive control, with consistent staining throughout each specimen. The extent of HSPG immunoreactivity in cancer decreased with increasing Gleason grade (measured as percent of acini staining, in 10% increments; p = 0.002). These findings indicate that HSPG is a consistent component of the basement membrane of benign, hyperplastic, and early neoplastic prostatic acini, and, unlike other extracellular matrix proteins such as type IV collagen, is not hindered by background staining around stromal smooth muscle cells. High grade PIN and well differentiated adenocarcinoma usually maintain an intact basement membrane, and loss of the basement membrane occurs with histologic dedifferentiation.